Systems and methods using paramagnetic agents for in vitro diagnostic applications

ABSTRACT

The present invention discloses a method and systems for detecting a target biochemical molecular species whose main component is water. In one aspect, the method comprises steps of: (a) obtaining a sample whose main component is water; (b) providing Functionalized Paramagnetic Particles (FPP) comprising a paramagnetic core and a moiety configured to interact with the target biochemical molecular species; (c) contacting the FPP with the sample; (d) exposing the sample to an applied magnetic field; (e) measuring a change in a nuclear relaxation property of the sample, caused by the interaction between the FPP and the biochemical molecular species in the applied magnetic field; and (f) correlating the change to the presence of the biochemical molecular species in the sample. According to a main aspect of the invention, a change in T.sub.1 nuclear relaxation property of the water protons in the sample is correlated to the presence of the target biochemical molecular species.

This application is a Divisional of U.S. application Ser. No.14/090,298, filed Nov. 26, 2013, which is incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to the field of magnetic resonance-basedsystems and related methods, for diagnostic in vitro applications, andmore particularly, to systems that use magnetic resonance ¹H-relaxometryfor detection of a biomarker of interest and methods thereof.

BACKGROUND OF THE INVENTION

Biomarkers are objective measures or indicators which are used toevaluate disease versus normal biological processes or responses to adrug or treatment. Many different biomarker types are utilized forvarious purposes in the pharmaceutical process. Biomarker types andapplications thereof are broadly used in the clinical and healthcarespectrum, for example biomarkers for risk assessment, permit theestimation of the risk of an individual to develop a particular disease.Other types of biomarkers include: biomarkers for earlier and morespecific indication of a compound's toxicity; biomarkers for prognosis(providing information about the expected course of a disease);biomarkers for patient stratification (allowing to identify the besttreatment for a disease); and, biomarkers for therapy monitoring(providing information at an early stage as to whether treatment isworking or if the disease is getting worse).

Biosensing strategies using magnetic nanoparticles have been reported inthe relevant art. These publications describe magnetic resonance-relatedtechniques based on T₂-relaxation time measurements. For example, USapplication No. 2011/0091987A1 and a recently published scientificarticle (Huilin Shao et al., Theranostics 2012) describe NMR-baseddetection mechanism for diagnostic applications. In order to increasethe sensitivity of the detection, magnetic nanoparticles have been usedthat are specifically designed and shown to improve T2* changes. Theseparticles consist of ferrite particles or crossed linked iron oxide.

Thus, there is still a long felt need to provide sensitive and reliablemeans and methods for the identification and quantification of abiomarker of interest for diagnostic applications.

SUMMARY OF THE INVENTION

It is an object of the present invention to disclose a method fordetecting a target biochemical molecular species or at least oneproperty correlated with the occurrence of said biochemical molecularspecies in a sample whose main component is water, comprising;

-   a. obtaining a sample whose main component is water;-   a. providing Functionalized Paramagnetic Particles (FPP) comprising    a paramagnetic core and a moiety configured to interact with said    target biochemical molecular species or with molecules collectively    reporting on a property of said target biochemical molecular    species;-   a. contacting said FPP with said sample;-   a. exposing said sample to an applied magnetic field; and,-   a. measuring a change in a nuclear relaxation property of said    sample, caused by said interaction between said FPP and said    biochemical molecular species or said molecules collectively    reporting on a property of said target biochemical molecular    species; in the applied magnetic field; and,-   a. correlating said change to the presence of said biochemical    molecular species in said sample or to at least one property    correlated with the occurrence of said biochemical molecular species    in said sample;    wherein a change in T.sub.1 nuclear relaxation property of the water    protons in said sample is correlated to the presence of said target    biochemical molecular species or to at least one property correlated    with the occurrence of said biochemical molecular species in said    sample, further wherein said FPP comprises a non ferrous oxide    paramagnetic core.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of performing two or moremeasurements to determine the relaxation time of the sample, wherein themeasurements are performed before and after at least one addition ofsaid FPP.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of detecting said targetbiochemical molecular species and/or characterizing at least oneproperty correlated with the occurrence of said biochemical molecularspecies in vitro.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of forming said FPP as asingle molecule, a multimeric system, a micro-sized vesicle or particle,a nano-sized vesicle or particle, a liposome, a probe or any combinationthereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said samplefrom a group consisting of a liquid, a gas, a slurry, a liquidcontaining particulates, a gas containing particulates, a gel, a sol, asuspension, a solution, a dispersion, a colloid, a mixture, an emulsion,an aerosol, a liquid containing solid objects, a gas containing solidobjects, and any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said samplefrom a group comprising a biological fluid, a biological tissue, atissue extract, an industrial fluid, food sample, a beverage, wine,water, potable water, sewage, irrigation water, sea water, river water,lake water, industrial effluent, farm effluent, effluent from humanhabitation, road runoff, cleaning fluid, a gas sample or any combinationthereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting saidbiological fluid from a group comprising urine, blood, lymph, plasma,cerebrospinal fluid, saliva, amniotic fluid, bile and tears.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of providing said samplewithin a production process.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting saidproduction process in an industrial area, said industrial area is amember of a group consisting of the pharmaceuticals, food production,beverage production, chemical refining, chemical processing, medicalproducts, biological products, metal casting, metal refining,desalination, fluid purification, and sewage processing.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of analyzing at least onecharacteristic or property of said target molecular species, saidcharacteristic or property is selected from a group comprisingconcentration, permeability, oxidation state, redox characteristic(reduction-oxidation state), activation state and any combinationthereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of applying a magneticfield, thereby enhancing the change in a paramagnetic nuclear relaxationproperty of said sample upon comparing relaxation rates at two differentmagnetic fields.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of measuring a change in anuclear relaxation property of said sample using a portable NMR or MRImeasuring means.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of measuring a change in anuclear relaxation property of said sample using a magnetic resonancedevice (MRD) consisting of magnets housed within a cage.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of measuring a change in anuclear relaxation property of said sample using a self-fastening cagetype of a magnetic resonance device (MRD).

It is another object of the present invention to disclose the method asdefined above, In a self-fastening cage of a magnetic resonance device(MRD) (300), a method according to claim 1 comprising an additional stepof providing a homogeneous, stable and uniform magnetic field therein,further wherein said self-fastening cage type MRD additionallycharacterized by an outside shell comprising at least threeflexi-jointed superimposed walls (1).

It is another object of the present invention to disclose in aself-fastening cage type MRD (300), a method as defined above comprisingan additional step of providing an MRD characterized by an outsideshell; said outside shell comprising at least three flexi-jointedsuperimposed walls (1) disposed in a predetermined clockwise orcounterclockwise arrangement; said MRD comprising:

-   a. at least six side-magnets (2) arranged in two equal groups being    in a face-to-face orientation in a magnetic connection with said    outside shell, increasing the overall strength of the magnetic field    provided in said cage;-   b. at least two pole-magnet pieces (3), arranged in a face-to-face    orientation in between said side-magnets (2);-   c. at least two main-magnets (4), located on said pole-pieces (3),    arranged in a face-to-face orientation, generating the static    magnetic field therein said cage; and,-   d. shimming mechanism, said mechanism is selected from a group    consisting of an array of active shim coils, passive shimming    elements or a combination thereof;    wherein at least a portion of said side-magnets (2) are    superconductors or ferromagnets.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of providing a magneticresonance device adapted to producing high contrast high resolutionimages of said sample.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of providing a magneticresonance device comprising:

-   a. an envelope for least partially confining said sample;-   b. a plurality of magnets located at least partially around said    envelope, said plurality of magnets comprising:    -   i. a least one first magnet configured to provide a high        magnetic field for generating multiple time-resolved one or more        first images at high resolution of at least a portion of said        sample; and    -   ii. a least one second magnet configured to provide a low        magnetic field for generating multiple time-resolved one or more        second images at high contrast of at least portion of same said        sample; wherein at least one image of said first images and at        least one image of said second images being generated in a time        no greater than approximately the time between two first images;        and,-   c. a CPU to process said images comprising a computer readable    medium containing instructions for generating at least one third    image superimposing at least one image of said first images with at    least one image of said second images.

It is another object of the present invention to disclose the method asdefined above, comprising additional steps of

-   a. generating multiple time resolved one or more first images at    high resolution of at least a portion of said sample;-   b. generating multiple time resolved one or more second images at    high contrast of at least portion of same said sample; and-   c. superimposing at least one image of said first images with at    least one image of said second images;    whereby a high-contrast, high resolution real-time continuous image    of said sample is obtained.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said at leastone first magnet to be of 2 Tesla and lower.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said at leastone first magnet to be of 2 Tesla and higher.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said at leastone first magnet from a group consisting of permanent magnets,electromagnets, superconducting magnets, and any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said at leastone second magnet to be of 2 Tesla and lower.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said at leastone second magnet to be of 2 Tesla and higher.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said at leastone second magnet from a group consisting of permanent magnets,electromagnets, superconducting magnets, and any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of generating a magneticresonance signal in the range of about 0.1 Tesla and about 10 Tesla.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of generating a magneticresonance signal in the range of 2 Tesla and lower.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of generating a magneticresonance signal in the range of 2 Tesla and higher.

It is another object of the present invention to disclose the method asdefined above, further comprises steps of applying a magnetic resonancefrequency in the range of about 5 MHz to about 40 MHz.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said magnetsfrom a group consisting of permanent magnets, electromagnets,superconducting magnets, and any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said moietyfrom a group comprising antibodies, antibody fragments, monoclonalantibody, receptors, ligands, macromolecules, peptides, hormones, fattyacids, lipids, receptor agonists and antagonists, amino acids, sugars,lectins, albumins, polycarbon molecules, glycoproteins, nucleic acids,pegylated molecules, liposomes, chelators, cells, viruses,chemotherapeutic agents and any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said targetbiochemical molecular species from a group comprising a biologicalmolecule, a chemical molecule, an analyte, a contaminant, a particle, apathogen or any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said targetbiochemical molecular species from a group comprising a protein, apathogen, a prion, a virus, a bacteria, a contaminant, a pathologicalisoform, a biomarker, an allergen, a neurotransmitter, an antigenicdeterminant, an epitope, a cell marker, cell membrane marker or epitope,a membrane marker, an enzyme, a chemical molecule, an analyte, areceptor, a ligand, a macromolecule, a peptide, a hormone, a fatty acid,a lipid, a receptor agonist and antagonist, an amino acid, a sugar, aglycoprotein, a nucleic acid, an antioxidant agent, a chemotherapeuticagent, a biological tissue and any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said analytefrom a group comprising an organic analyte and an inorganic analyte.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said inorganicanalyte from a group comprising molecular oxygen, oxygen-containingradicals and combinations thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of detectingoxygen-containing radicals “ad hoc” generated, for assessing theanti-oxidant properties of the sample.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting saidparamagnetic core as a metal ion, a metal complex, oxides of a metalion, oxides of a transition metal, mixed oxides of a transition metaland their mixtures.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting saidparamagnetic core from a group comprising metal complexes, aggregates ofmetal complexes, polymer-bound metal complexes, stable organic radicalsand any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said metal ionfrom a group comprising an ion of nickel, iron, manganese, copper,gadolinium, europium and mixtures thereof.

It is another object of the present invention to disclose the method asdefined above, based on a competition assay for assessing redoxcharacteristics, comprising steps of detecting differences inParamagnetic Relaxation Enhancement (PRE) properties induced by a changein at least one redox characteristic of said FPP, using an appliedmagnetic field.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said redoxcharacteristic from a group comprising lipid peroxidation, lipidperoxidation followed by a change in membrane permeability, redoxpotential of metal ions, formation and cleavage of disulfide bonds,oxidation state, antioxidant activity and any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of providing said FPP as aliposome loaded with a plurality of paramagnetic payloads.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of applying a magneticfield, thereby enhancing a change in the permeability of said liposomeso as to affect a nuclear relaxation property of said sample.

It is another object of the present invention to disclose the method asdefined above, further comprising steps of applying a magnetic field,thereby enhancing a change in at least one of cleavage or formation ofdisulfide bonds of said moiety so as to affect a nuclear relaxationproperty of said sample.

It is another object of the present invention to disclose the method asdefined above, further comprising steps of applying a magnetic field,thereby affecting at least one property of said FPP selected from agroup comprising concentration, lipid peroxidation, membranepermeability, redox potential, formation and cleavage of disulfidebonds, oxidation state, redox potential, activation state, bindingaffinity, and any combination thereof, so as to induce a change in anuclear relaxation property of said sample.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of conjugating saidliposome with a site-specific ligand.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of conjugating saidliposome with a biotin activated molecule.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of providing said FPP as abiotinylated liposome.

It is an object of the present invention to disclose a method fordetection of a biomarker in a sample whose main component is water,comprising steps of:

-   a. obtaining a sample whose main component is water;-   b. providing liposomes loaded with a plurality of paramagnetic    agents, said liposomes are conjugated with a site specific moiety    configured to interact with said biomarker in said sample;-   c. contacting said liposomes with said sample under conditions that    allow the interaction between the site specific moiety and said    biomarker;-   d. exposing said sample to an applied magnetic field; and,-   e. measuring a change in a nuclear relaxation property of said    sample caused by said interaction between the liposomes and said    biomarker in the applied magnetic field;    wherein a change in T.sub.1 nuclear relaxation property is    correlated to the presence of said biomarker in said sample.

It is another object of the present invention to disclose the method asdefined above, comprising additional steps of:

-   a. providing biotinylated liposomes; said liposomes loaded with a    plurality of paramagnetic agents;-   b. providing biotinylayed ligands, said ligands configured to    interact with said biomarker;-   c. providing activated avidin molecules;-   d. contacting said biotinylated liposomes, said biotinylayed ligands    and said activated avidin molecules with said sample so as to enable    avidin-biotin interaction, thereby forming complexes comprising said    liposomes, said ligand and said biomarker; such that said complexes    are specific to said biomarker; and,-   e. measuring a change in a nuclear relaxation property of said    sample caused by said complex formation in the applied magnetic    field;    wherein a change in T.sub.1 nuclear relaxation property is    correlated to the presence of said biomarker in said sample.

It is an object of the present invention to disclose a system fordetecting a target biochemical molecular species or at least oneproperty correlated with the occurrence of said biochemical molecularspecies in a sample whose main component is water, comprising;

-   a. a magnetic resonance device (MRD) configured to measure a change    in nuclear relaxation property of said sample; and,-   b. a plurality of Functionalized Paramagnetic Particles (FPP) said    FPP comprising a paramagnetic core and a moiety configured to    interact with said target biochemical molecular species or with    molecules collectively reporting on a property of said target    biochemical molecular species;    wherein a change in T.sub.1 nuclear relaxation property of water    protons in said sample measured by said MRD is correlated to the    presence of said target biochemical molecular species and/or to the    at least one property correlated with the occurrence of said    biochemical molecular species in said sample, further wherein said    FPP comprises a non ferrous oxide paramagnetic core.

It is another object of the present invention to disclose the system asdefined above, further comprises means for detecting said targetbiochemical molecular species and/or characterizing at least oneproperty correlated with the occurrence of said biochemical molecularspecies in vitro.

It is another object of the present invention to disclose the system asdefined above, wherein said FPP is formed as a single molecule, amultimeric system, a micro-sized vesicle or particle, a nano-sizedvesicle or particle, a liposome, a probe and any combination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said sample is selected from a group consistingof a liquid, a gas, a slurry, a liquid containing particulates, a gascontaining particulates, a gel, a sol, a suspension, a solution, adispersion, a colloid, a mixture, an emulsion, an aerosol, a liquidcontaining solid objects, a gas containing solid objects, and anycombination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said sample is further selected from a groupcomprising a biological fluid, a biological tissue, a tissue extract, anindustrial fluid, food sample, a beverage, wine, water, potable water,sewage, irrigation water, sea water, river water, lake water, industrialeffluent, farm effluent, effluent from human habitation, road runoff,cleaning fluid, a gas sample or any combination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said biological fluid is selected from a groupcomprising urine, blood, lymph, plasma, cerebrospinal fluid, saliva,amniotic fluid, bile and tears.

It is another object of the present invention to disclose the system asdefined above, wherein said sample is provided within a productionprocess.

It is another object of the present invention to disclose the system asdefined above, wherein said production process is in an industrial area,said industrial area is a member of a group consisting of thepharmaceuticals, food production, beverage production, chemicalrefining, chemical processing, medical products, biological products,metal casting, metal refining, desalination, fluid purification, andsewage processing.

It is another object of the present invention to disclose the system asdefined above, wherein said property is selected from a group comprisingconcentration, permeability, oxidation state, redox characteristic(reduction-oxidation state), activation state and any combinationthereof.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device (MRD) isconfigured to enhance the change in a paramagnetic nuclear relaxationproperty of said sample upon comparing relaxation rates at two differentmagnetic fields.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device (MRD) is aportable NMR or MRI measuring means.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device (MRD) consists ofmagnets housed within a cage.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device (MRD) is aself-fastening cage type of a magnetic resonance device (300).

It is another object of the present invention to disclose in aself-fastening cage of a magnetic resonance device (MRD) (300), a systemas defined above wherein said self-fastening cage type MRD additionallycharacterized by an outside shell comprising at least threeflexi-jointed superimposed walls (1).

It is another object of the present invention to disclose n aself-fastening cage type MRD (300), a system as defined above furthercomprises a MRD characterized by an outside shell; said outside shellcomprising at least three flexi-jointed superimposed walls (1) disposedin a predetermined clockwise or counterclockwise arrangement; said MRDcomprising:

-   a. at least six side-magnets (2) arranged in two equal groups being    in a face-to-face orientation in a magnetic connection with said    outside shell, increasing the overall strength of the magnetic field    provided in said cage;-   b. at least two pole-magnet pieces (3), arranged in a face-to-face    orientation in between said side-magnets (2);-   c. at least two main-magnets (4), located on said pole-pieces (3),    arranged in a face-to-face orientation, generating the static    magnetic field therein said cage; and,-   d. shimming mechanism, said mechanism is selected from a group    consisting of an array of active shim coils, passive shimming    elements or a combination thereof;    wherein at least a portion of said side-magnets (2) are    superconductors or ferromagnets.

It is another object of the present invention to disclose the system asdefined above, wherein said MRD is configured to produce high contrasthigh resolution images of said sample.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device comprising:

-   a. an envelope for least partially confining said sample;-   b. a plurality of magnets located at least partially around said    envelope, said plurality of magnets comprising:    -   i. a least one first magnet configured to provide a high        magnetic field for generating multiple time-resolved one or more        first images at high resolution of at least a portion of said        sample; and    -   ii. a least one second magnet configured to provide a low        magnetic field for generating multiple time-resolved one or more        second images at high contrast of at least portion of same said        sample; wherein at least one image of said first images and at        least one image of said second images being generated in a time        no greater than approximately the time between two first images;        and,-   c. a CPU to process said images comprising a computer readable    medium containing instructions for generating at least one third    image superimposing at least one image of said first images with at    least one image of said second images, whereby a high contrast, high    resolution real time continues image of said sample is obtained.

It is another object of the present invention to disclose the system asdefined above, wherein said at least one first magnet is of 2 Tesla andlower.

It is another object of the present invention to disclose the system asdefined above, wherein said at least one first magnet is of 2 Tesla andhigher.

It is another object of the present invention to disclose the system asdefined above, wherein said at least one first magnet is selected from agroup consisting of permanent magnets, electromagnets, superconductingmagnets, and any combination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said at least one second magnet is of 2 Tesla andlower.

It is another object of the present invention to disclose the system asdefined above, wherein said at least one second magnet is of 2 Tesla andhigher.

It is another object of the present invention to disclose the system asdefined above, wherein said at least one second magnet is selected froma group consisting of permanent magnets, electromagnets, superconductingmagnets, and any combination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device (MRD) isconfigured to generate a magnetic resonance signal in the range of about0.1 Tesla and about 10 Tesla.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device (MRD) isconfigured to generate a magnetic resonance signal in the range of 2Tesla and lower.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device (MRD) isconfigured to generate a magnetic resonance signal in the range of 2Tesla and higher.

It is another object of the present invention to disclose the system asdefined above, wherein said magnetic resonance device (MRD) isconfigured to generate a magnetic resonance frequency in the range ofabout 5 MHz to about 40 MHz.

It is another object of the present invention to disclose the system asdefined above, wherein said magnets are selected from a group consistingof permanent magnets, electromagnets, superconducting magnets, and anycombination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said moiety is selected from a group comprisingantibodies, antibody fragments, monoclonal antibody, receptors, ligands,macromolecules, peptides, hormones, fatty acids, lipids, receptoragonists and antagonists, amino acids, sugars, lectins, albumins,polycarbon molecules, glycoproteins, nucleic acids, pegylated molecules,liposomes, chelators, cells, viruses, chemotherapeutic agents and anycombination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said target biochemical molecular species isselected from a group comprising a biological molecule, a chemicalmolecule, an analyte, a contaminant, a particle, a pathogen or anycombination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said target biochemical molecular species isselected from a group comprising a protein, a pathogen, a prion, avirus, a bacteria, a contaminant, a pathological isoform, a biomarker,an allergen, a neurotransmitter, an antigenic determinant, an epitope, acell marker, cell membrane marker or epitope, a membrane marker, anenzyme, a chemical molecule, an analyte, a receptor, a ligand, amacromolecule, a peptide, a hormone, a fatty acid, a lipid, a receptoragonist and antagonist, an amino acid, a sugar, a glycoprotein, anucleic acid, an antioxidant agent, a chemotherapeutic agent, abiological tissue and any combination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said analyte is selected from a group comprisingan organic analyte and an inorganic analyte.

It is another object of the present invention to disclose the system asdefined above, wherein said inorganic analyte is selected from a groupcomprising molecular oxygen, oxygen-containing radicals and combinationsthereof.

It is another object of the present invention to disclose the system asdefined above, wherein said oxygen-containing radicals are “ad hoc”generated radicals, for assessing the anti-oxidant properties of thesample.

It is another object of the present invention to disclose the system asdefined above, wherein said paramagnetic core is selected from a groupcomprising a metal ion, a metal complex, oxides of a metal ion, oxidesof a transition metal, mixed oxides of a transition metal and theirmixtures.

It is another object of the present invention to disclose the system asdefined above, wherein said metal ion is selected from a groupcomprising an ion of nickel, iron, manganese, copper, gadolinium,europium and mixtures thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said redox characteristic is selected from agroup comprising lipid peroxidation, lipid peroxidation followed by achange in membrane permeability, redox potential of metal ions,formation and cleavage of disulfide bonds, oxidation state, antioxidantactivity and any combination thereof.

It is another object of the present invention to disclose the system asdefined above, wherein said FPP is a liposome loaded with a plurality ofparamagnetic payloads.

It is another object of the present invention to disclose the system asdefined above, comprising means for enhancing a change in thepermeability of said liposome so as to affect a nuclear relaxationproperty of said sample.

It is another object of the present invention to disclose the system asdefined above, wherein said system is adapted to detect a change in atleast one of cleavage or formation of disulfide bonds of said moiety soas to affect a nuclear relaxation property of said sample.

It is another object of the present invention to disclose the system asdefined above, wherein said property correlated with the occurrence ofsaid biochemical molecular species is selected from a group comprisingconcentration, lipid peroxidation, membrane permeability, redoxpotential, formation and cleavage of disulfide bonds, oxidation state,redox potential, activation state, binding affinity, and any combinationthereof.

It is another object of the present invention to disclose the system asdefined above, wherein said liposome is conjugated with a site-specificligand.

It is another object of the present invention to disclose the system asdefined above, wherein said liposome is conjugated with a biotinactivated molecule.

It is another object of the present invention to disclose the system asdefined above, wherein said FPP is a biotinylated liposome.

It is an object of the present invention to disclose a system fordetection of a biomarker in a sample, whose main component is water,comprising:

-   a. a sample whose main component is water;-   b. liposomes loaded with a plurality of paramagnetic agents, said    liposomes are conjugated with a site specific moiety configured to    interact with said biomarker in said sample;-   c. a magnetic resonance device (MRD) configured to measure a change    in a nuclear relaxation property of a sample whose main component is    water removed from said production batch or continuous flow of said    FBW or biological fluid;    wherein a change in T.sub.1 nuclear relaxation property of the water    protons in said sample is correlated to the presence of said    biomarker in said sample.

It is an object of the present invention to disclose the use ofFunctionalized Paramagnetic Particles (FPP) to detect the presence or atleast one other characteristic of a target biochemical molecular specieswithin a sample whose main component is water, said FPP comprising aparamagnetic core and a moiety configured to interact with said targetbiochemical molecular species or with molecules collectively reportingon a property of said target biochemical molecular species; wherein achange in T.sub.1 nuclear relaxation property of water protons withinsaid sample measured by a generated applied magnetic field is correlatedto the presence or at least one other characteristic of said targetbiochemical molecular species in said sample.

It is an object of the present invention to disclose the use as definedabove further adapted to detect at least one property correlated withthe occurrence of said biochemical molecular species in said sample.

It is an object of the present invention to disclose a method ofestablishing the redox properties of a production batch or continuousflow of a Foodstuff, Beverage or Wine (FBW) or of a biological fluid,comprising the steps of:

-   a. obtaining a sample removed from said production batch or    continuous flow of said FBW or from said biological fluid;-   b. providing Functionalized Paramagnetic Particles (FPP) configured    to change their redox property upon interaction with dissolved    molecular oxygen or “ad hoc” generated radicals of said removed    sample;-   c. contacting said FPP with said removed sample;-   d. exposing said removed sample to an applied magnetic field; and,-   e. measuring a change in a nuclear relaxation property of said    removed sample caused by said change in the redox properties of said    FPP in the applied magnetic field;    wherein a change in T.sub.1 nuclear relaxation property is    correlated with the presence and/or concentration of said molecular    oxygen or of the “ad hoc” generated radicals of said removed sample,    thereby establishing the redox properties of said production batch    or continuous flow of said FBW or of said biological fluid.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of providing said FPPconjugated with at least one moiety configured to interact withdissolved molecular oxygen or with “ad hoc” generated radicals.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said moietyfrom a group comprising a lipid, a fatty acid, an amino acid, a peptide,a protein, a molecule containing at least one disulfide bond, a liposomeand any combination thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of measuring a change in anuclear relaxation property of said sample caused by a change in theantioxidant activity of said removed sample in the applied magneticfield.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of measuring a differencein Paramagnetic Relaxation Enhancement (PRE) property of said removedsample caused by said interaction of said FPP with said dissolvedmolecular oxygen or with said “ad hoc” generated radicals.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of contacting said removedsample with FPP configured to form a liposome structure, said FPPcomprising a paramagnetic core and a fatty acid moiety, whereinperoxidation of said fatty acid moiety substantially changes thepermeability of said liposome.

It is an object of the present invention to disclose the method asdefined above, comprising an additional step of measuring a change in anuclear relaxation property of said removed sample based on competitionfor molecular oxygen consumption.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of providing said FPPcomprising a paramagnetic core selected from a group comprising a metalion, a metal complex, oxides of a metal ion, oxides of a transitionmetal, mixed oxides of a transition metal and their mixtures.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting said metal ionfrom a group comprising an ion of nickel, iron, manganese, copper,gadolinium, dysprosium, europium and mixtures thereof.

It is another object of the present invention to disclose the method asdefined above, comprising an additional step of selecting saidbiological fluid from a group comprising urine, blood, lymph, plasma,cerebrospinal fluid, saliva, amniotic fluid, bile and tears.

It is an object of the present invention to disclose a system forestablishing the redox properties of a production batch or continuousflow of a Foodstuff, Beverage, Wine (FBW) or of a biological fluid,comprising:

-   a. a magnetic resonance device (MRD) configured to measure a change    in a nuclear relaxation property of a sample removed from said    production batch or continuous flow of said FBW or of said    biological fluid; and,-   b. a plurality of Functionalized Paramagnetic Particles (FPP)    configured to be in contact with said removed sample, said plurality    of FPP are further configured to change at least one of their redox    properties upon interaction with dissolved molecular oxygen or with    “ad hoc” generated radicals of said removed sample;    wherein a change in T.sub.1 nuclear relaxation property measured by    said MRD is correlated to the presence or concentration of dissolved    molecular oxygen or “ad hoc” generated radicals of said removed    sample, thereby the redox properties of said production batch or    continuous flow of said FBW or of said biological fluid are    established.

It is another object of the present invention to disclose the system asdefined above, wherein said biological fluid is selected from a groupcomprising urine, blood, lymph, plasma, cerebrospinal fluid, saliva,amniotic fluid, bile and tears.

It is another object of the present invention to disclose a system forestablishing the potability of a production batch or continuous flow ofa flowable Foodstuff, Beverage or Wine (FBW), comprising:

-   a. a magnetic resonance device (MRD) configured to measure a change    in nuclear relaxation property of a sample removed from said    production batch or continuous flow of said flowable FBW; and,-   b. a plurality of functionalized paramagnetic particles (FPP)    configured to be in contact with said sample, said plurality of FPP    are further configured to change their redox/oxidative properties    upon interaction with dissolved molecular oxygen or “ad hoc”    generated radicals of said removed sample;    wherein a change in T.sub.1 nuclear relaxation property measured by    said MRD correlates with dissolved molecular oxygen or “ad hoc”    generated radicals concentration of said FBW sample, thereby    establishing the potability of said production batch or continuous    flow of said flowable FBW.

It is another object of the present invention to disclose the system asdefined above, wherein a concentration value lower than about 6 ml ofdissolved oxygen per liter of said removed sample is indicative of thepotability of said production batch or continuous flow of said FBW.

It is another object of the present invention to disclose the system asdefined above, wherein a value lower than X ml of oxygen per liter iscorrelated to >7 of the 9 point hedonic scale.

It is another object of the present invention to disclose the system asdefined above, wherein a value lower than X ml of oxygen per liter iscorrelated to >y of the hybrid scale.

It is another object of the present invention to disclose the system asdefined above, wherein a value lower than X ml of oxygen per liter iscorrelated to >y of the self-adjusting scale.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to understand the invention and to see how it may beimplemented in practice, several embodiments will now be described, byway of non-limiting example only, with reference to the accompanyingdrawing, in which

FIG. 1: is a schematic illustration of one embodiment of the system forassessment of cell epitopes, disclosed in the present invention;

FIG. 2: is a schematic illustration of a further embodiment of thesystem for assessment of cell epitopes, disclosed in the presentinvention;

FIG. 3: is a schematic diagram illustrating steps for assessment of cellreceptors according to an embodiment of the present invention;

FIG. 4: is a graphic representation of relaxivity results at differentproton larmor frequencies;

FIG. 5: is a graphic representation showing relaxation rate by Mn(II)ion concentration;

FIG. 6: is a schematic illustration of a process for preparation ofparamagnetic liposomes according to an embodiment of the presentinvention;

FIG. 7: schematically presents a partial sectional top and out of scaleview, with respect to an axial plane of the MRD (300) wherein the shapeof a square parallelepiped is provided, having four cage walls (1), fourside magnets (2); and a pole-piece (3); said cage walls and side-magnetsare essentially interconnected in a superimposed manner such that aself-fastening cage is obtained;

FIG. 8: schematically presents an entire perspective view of the of the3D MRD (300), having two cage walls (1), eight side magnets (2); twopole-pieces (3); two main magnet (4) and eight square corner-magnets (5)and four cylinder corner-magnets located inside the pole-pieces; all ofthem are arranged in two equal groups face-to-face orientation; and,

FIG. 9: schematically illustrates an embodiment with a high contrast,high resolution magnetic resonance device.

DETAILED DESCRIPTION OF THE INVENTION

The following description is provided, alongside all chapters of thepresent invention, so as to enable any person skilled in the art to makeuse of said invention and sets forth the best modes contemplated by theinventor of carrying out this invention. Various modifications, however,will remain apparent to those skilled in the art, since the genericprinciples of the present invention have been defined specifically toprovide a method for detection of a biochemical molecular species in asample and a system thereof.

Assessment of markers can be pursued by a number of techniques andNMR/MRI is one of them. The detection of a biomarker implies the use ofa probe that binds or is responsive to the given biomarker. The probeacts as reporter in the selected NMR/MRI modality. A modality endowedwith high sensitivity which is represented by ¹H-Relaxometry as themeasured signal arising from the “bulk” water solvent, is provided bythe present invention. By this approach one measures the effect of theresponsiveness of the probe on specific properties of the water ¹Hresonance in the presence of the biomarker of interest. T₁, T₂ and T₂*are the parameters that may be taken in consideration in the hereinprovided ¹H-relaxometric assay.

According to one embodiment, the present invention provides a method fordetecting a target biochemical molecular species in a sample, especiallya sample whose main component is water, comprising; (a) obtaining asample; (b) providing Functionalized Paramagnetic Particles (FPP)configured to interact with said target biochemical molecular species,each FPP comprising a paramagnetic core and a moiety configured tointeract with said target biochemical molecule or a set of biochemicalmolecules collectively defining a property of the specimen; (c)contacting said FPP with said sample under conditions that allow theinteraction between said FPP and said biochemical molecular species; (d)exposing said sample to an applied magnetic field; and, (e) measuring achange in a nuclear relaxation property of water protons of said samplecaused by said interaction between said FPP and said biochemicalmolecular species, in the applied magnetic field. In a core aspect ofthe invention, a change in T.sub.1 nuclear relaxation property of waterprotons is correlated to the presence of said target biochemicalmolecular species in said sample and/or to at least one propertyassociated with the occurrence of said biochemical molecular species insaid sample. In a further embodiment of the invention, the FPP comprisesa particle made of a non ferrous oxide paramagnetic core.

In a further embodiment, the present invention provides A method fordetecting a target biochemical molecular species or at least oneproperty correlated with the occurrence of said biochemical molecularspecies in a sample whose main component is water, comprising; (a)obtaining a sample whose main component is water; (b) providingFunctionalized Paramagnetic Particles (FPP) comprising a paramagneticcore and a moiety configured to interact with said target biochemicalmolecular species or with molecules collectively reporting on a propertyof said target biochemical molecular species; (c) contacting said FPPwith said sample; (d) exposing said sample to an applied magnetic field;and, (e) measuring a change in a nuclear relaxation property of saidsample, caused by said interaction between said FPP and said biochemicalmolecular species or said molecules collectively reporting on a propertyof said target biochemical molecular species; in the applied magneticfield; and, (f) correlating said change to the presence of saidbiochemical molecular species in said sample or to at least one propertycorrelated with the occurrence of said biochemical molecular species insaid sample; wherein a change in T.sub.1 nuclear relaxation property ofthe water protons in said sample is correlated to the presence of saidtarget biochemical molecular species or to at least one propertycorrelated with the occurrence of said biochemical molecular species insaid sample, further wherein said FPP comprises a non ferrous oxideparamagnetic core.

It is herein disclosed that according to a main embodiment, the presentinvention uniquely combines NMR relaxometer technology, preferably aportable NMR device, with an amplification procedure for thequantification of a biomarker or biochemical molecule or biochemicalmolecular species of interest. The present invention provides a novelrelaxometric assay based on appropriately designed functionalizedparamagnetic particles (FPP), preferably liposomes, containing aparamagnetic core or paramagnetic species and a moiety/moieties, whichis/are specifically designed to interact and/or be responsive to thetarget biomarker or biochemical molecular species or analyte ofinterest.

The use of paramagnetic species allows determining differentconcentrations of i.e. a biomarker or analyte of interest within thetested sample, thus affecting for example the assessment between healthyand diseased tissues. Gadolinium (Gd)-based contrast agents are the mostused systems. The development of new Gd-based or other metal ioncontrast agents with high relaxation enhancement ability and targetingcapability is a further aspect of the present invention. It is alsowithin the scope of the present invention to set-up innovative molecularmagnetic resonance protocols. These protocols are capable of detectingepitopes that are present at very low concentrations (typically in the50-100 nmol/L range) and therefore it is necessary to design propermeans and methods to amplify the response upon recognition of the targetmolecule of interest.

According to one aspect, the present invention provides a magneticresonance-relaxometric assay and system adapted to measure small volumeof samples.

According to certain aspects of the present invention, automated systems(i.e. a processor) and procedures are herein provided configured todetermining a change in nuclear relaxation properties of a samplecontaining a target biochemical molecule or biochemical molecularspecies of interest. These automated systems and procedures are furthercapable of correlating the measured change in the nuclear relaxationenhancement with the quantification of the target biochemical moleculeor biochemical molecular species or an overall property of interestwithin said sample.

It is further within the scope of the present invention to disclosemeans and methods for performing quality control of the producedfunctionalized paramagnetic particles and the T₁ measurements thatreports on a specific target biomarker or epitope of interest.

It is further within the scope of the present invention to disclosemeans and methods for detecting at least one property correlated withthe occurrence of a biochemical molecular species in a sample.

In a further embodiment of the invention the method as disclosed hereinfurther comprises steps of analyzing at least one characteristic orproperty of the target molecular species selected from a groupcomprising concentration, permeability, oxidation state, redoxcharacteristic (reduction-oxidation state), activation state and anycombination thereof.

As used herein the term ‘plurality’ applies hereinafter to any integergreater than or equal to one.

The term ‘about’ denotes ±25% of the defined amount or measure or value.

The term ‘biochemical molecule’ as used herein refers to any chemical orbiological molecule. Examples of chemical or biological moleculesincluded within the scope of the present invention may comprise, but arenot limited to: a protein, a pathogen, a prion, a virus, a bacteria, acontaminant, a pathological isoform, a biomarker, an allergen, aneurotransmitter, an antigenic determinant, an epitope, a cell marker,cell membrane marker or epitope, a membrane marker, an enzyme, achemical molecule, an analyte, a receptor, a ligand, a macromolecule, apeptide, a hormone, a fatty acid, a lipid, a receptor agonist andantagonist, an amino acid, a sugar, a glycoprotein, a nucleic acid, anantioxidant agent, a chemotherapeutic agent, a biological tissue and anycombination thereof.

The term ‘biochemical molecular species’ as used herein refers to abiological or chemical molecule as defined above or a set of biochemicalmolecules, collectively defining a property of a specimen or to one ormore biochemical molecules collectively reporting on a given property.It is within the disclosure of the present invention that the term‘biochemical molecular species’ refers to biochemical molecules that aresubstantially similar in their chemical and/or biological properties andtheir identification and quantification are of interest. In otherembodiments, the term ‘biochemical molecular species’ can be applied toan ensemble or family of chemically or biologically identical molecularentities that can explore the same set of chemical or biologicalcharacteristics.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of selecting the analyte froma group comprising an organic analyte and an inorganic analyte.

The term ‘particle’ refers hereinafter to any form comprising, but notlimited to, a single molecule, a multimeric molecule or system, amacromolecule, a monomer, an oligomer, a polymer, a vesicle, a nano ormicro sized vesicle, a liposome, a probe, a cell, a yeast cell or anycombination thereof.

The term ‘Functionalized Paramagnetic Particle’ or ‘FPP’ refershereinafter to a particle or probe containing a paramagnetic entity oragent or core and a moiety that is adapted to interact with a targetbiochemical molecular species or biomarker of interest.

In a preferred embodiment of the invention, the paramagnetic entity,agent, or core constitutes a non ferrous oxide metal ion. According tocertain embodiments, the paramagnetic entity, agent, or core comprise ametal ion, including oxides of a metal ion, oxides of a transitionmetal, mixed oxides of a transition metal and their mixtures. Morespecifically, the metal ion may be selected from a group comprising anion of nickel, manganese, copper, gadolinium, dysprosium, europium andmixtures thereof.

In another embodiment of the invention, the FPP may include a moiety orresidue adapted to specifically interact with a target biochemicalmolecular species or biomarker of interest. Such a moiety or residue maycomprise a receptor, ligand or any compound, such as a biomolecule or asmall molecule, an antibody or an antigen-binding fragment that bindsspecifically to a selected target molecule or analyte. In specificembodiments, a moiety or residue may comprise a macromolecule, apeptide, a hormone, a fatty acid, a lipid, a receptor agonist and/orantagonist, an amino acid, a sugar, lectins, albumins, polycarbonmolecules, glycoproteins, nucleic acids, pegylated molecules, liposomes,chelators, cells, viruses, chemotherapeutic agents, biotin, streptavidinand any combination thereof. In preferred embodiments of the invention,such functional moieties or residues as herein described are configuredto confer the FPP with molecular specificity, such that the change inthe measured T.sub.1 nuclear relaxation property correlates with thepresence and/or concentration of the target biochemical molecularspecies or biomarker of interest or to a collective property of thespecimen.

The term ‘paramagnetic core’ used herein refers hereinafter to aparamagnetic species or paramagnetic payload or paramagnetic entity orparamagnetic agent that may include a metal ion, a metal complex, oxidesof a metal ion, oxides of a transition metal, mixed oxides of atransition metal, metal complexes, aggregates of metal complexes,polymer-bound metal complexes, stable organic radicals and theirmixtures. The metal ion may be selected from a group comprising an ionof nickel, iron, manganese, copper, gadolinium, europium and mixturesthereof.

The term ‘nuclear relaxation property’ refers hereinafter to therelaxation of water protons. The effect is a change in magneticresonance signal, which is measured as a shortening of the longitudinal(T₁, spin-lattice) and transverse (T₂, spin-spin) relaxation times. Inone embodiment, the capacity of the paramagnetic species to decrease T₁and T₂ is respectively defined as the transverse and the longitudinalrelaxivities. It is herein acknowledged that T₁ values are longer athigher field strengths. Furthermore, the T₁ parameter is not affected byinternal magnetic field gradients or by differences in fluiddiffusivity. Moreover, instrument artifacts influence T₁ measurements toa much lesser degree than T₂ measurements.

Thus, in one aspect, the system and method of the present invention isdirected to detecting a biochemical molecule(s) or biochemical molecularspecies in a sample by measuring a change in the T₁ nuclear relaxationproperty of said sample, operated by an interaction betweenFunctionalized Paramagnetic Particles (FPP) and the biochemicalmolecular species, in the applied magnetic field. The aforementionedchange in T₁ nuclear relaxation property is correlated to the presenceof said target biochemical molecular species in said sample.

In another aspect, the invention is directed towards novel combinationsof T₁ and T₂ measurements, for example, to detect the presence and/orconcentration of a biochemical molecular species or analyte of interestin a sample. In one embodiment, these combinations of T₁ and T₂measurements may provide synergistic effects with respect to detectionand characterization of a target biochemical molecular species.

The term ‘ad hoc generated radicals’ as used herein refers to atoms,molecules, or ions with unpaired electrons or an open shellconfiguration, generated for, or as a result of, a particular or specialpurpose or end presently under consideration. Because of the unpairedelectrons, free radicals are highly chemically reactive. Free radicalsmay have positive, negative, or zero charge.

According to specific embodiments, the term ‘ad hoc generated radicals’relates to detecting generated oxygen-containing radicals using themeans and methods as described inter alia for assessing the anti-oxidantproperties of a sample of interest.

The term ‘correlated to’ or ‘correlates with’ refers hereinafter toeither a positive or negative dependence or connection or correspondencebetween two variables, parameters or sets of data, i.e. between themeasured change in nuclear relaxation property of an analysed sample andpresence or other characteristic of a target biochemical molecularspecies within said sample.

The term ‘non ferrous oxide’ is used hereinafter to indicate metalsother than iron and more particularly to oxides of ions that are notiron-based.

The term ‘portable’ applies hereinafter to any hand held or wearabledevices. The device can be carried or worn by the human body on a beltor in a pocket.

The term ‘self-fastening’ refers hereinafter to a strong magneticconnection between the side-magnets and the cage walls. The magnets'edges are attracted to each other such that a closed form is provided.The cage, magnetically attracted to the side-magnets, supports itselfwithout need for another connection.

The term ‘flexi-jointed’ refers hereinafter to the geometric arrangementof the cage walls wherein the joints of the walls are separated by anair gap, such that at least a portion of said walls is left free to moveand thus, if dislocation of one of the walls occurs, it is able tore-adjust so as to fit with adjacent (sometimes perpendicular) wall. Theflexi-jointed walls form the cage in such a manner that at least one ofits x, y or z dimensions is adjustable; hence a variation of the cagecontour, size or shape, e.g., cross section is obtained.

The term ‘superimposed’ refers hereinafter to the arrangement of thecage walls; each wall is placed over the other in an overlaying manner.

The term ‘magnetic resonance device’ (MRD) applies hereinafter to anyMagnetic Resonance Imaging (MRI) device, any Nuclear Magnetic Resonance(NMR) spectroscope, any Electron Spin Resonance (ESR) spectroscope, anyNuclear Quadrupole Resonance (NQR), any NMR relaxometer apparatus, or aportable NMR or MRI or any combination thereof.

The term ‘tolerance’ refers hereinafter to the interval between thecorner-magnets and the cage walls, enabling displacement of the walls.

The term ‘adjust’ applies hereinafter to a change of the magnet'sparameters before or after assembly, to optimize the magnetic fielduniformity.

The term ‘pole-piece’ applies hereinafter to an element of highpermeability material used to shape the uniformity of the magnetic fluxfrom a permanent magnet.

The term ‘side-magnets’ applies hereinafter to permanent magnetsarranged around the sides of pole-pieces.

The term ‘sample imaging units’ applies hereinafter to a device adaptedto provide a means of measuring the magnetic resonance of a samplewithin a uniform magnetic field.

The term ‘fluid imaging units’ applies hereinafter to a device adaptedto provide a means of measuring the magnetic resonance of a fluid samplewithin a uniform magnetic field.

The term ‘switching rate’ applies hereinafter to the number of separateddevices which are activated in a given time period.

The term ‘stratificated device’ refers hereinafter to any MRD 300 whichis characterized by more than two layers, forming more than twodetecting volumes,

-   e.g., in a top-and-bottom configuration and/or at least two adjacent    feeding streams carrying a plurality of objects in said    configuration.

The term ‘residue’ or ‘residues’ as used herein refers to any particleor particulate specific to a selected biological or chemical agent. Itis within the scope of the present invention that such a residue mayinclude, but it is not limited to a biomarker, a DNA, a protein, apeptide or any other part of a selected biological or chemical agent,particularly a pathogen.

The term ‘MRI contrast agents’ refers hereinafter in a non-limitingmanner to a compound or other substance introduced to the anatomical orfunctional region being imaged in order to enhance the contrast ofstructures, due to difference in the apparent density of various organsand tissues. Contrast agents are used in medical imaging studies to makeit easier to see the internal structures of the body. The addition ofcontrast agents in many cases improves sensitivity and/or specificity toimprove tissue discrimination in MRI. MRI contrast agents are classifiedby the different changes in relaxation times after their injection. Themost commonly used intravenous contrast agents are based on chelates ofgadolinium.

The term ‘rapidly’ refers herein to a time interval of less than 5minutes.

The term ‘nearly contemporaneously’ refers to a time interval less thanthe time interval between generation of successive first images.

It is thus one embodiment of the present invention to provide, a methodfor detecting a target biochemical molecular species in a sample,comprising; (a) obtaining a sample; (b) providing FunctionalizedParamagnetic Particles (FPP) configured to interact with said targetbiochemical molecular species of said sample, each FPP comprising aparamagnetic core and a moiety configured to interact with said targetbiochemical molecular species or a set of biomedical moleculescollectively defining a property of the specimen; (c) contacting saidFPP with said sample under conditions that allow the interaction betweensaid FPP and said biochemical molecular species or molecules; (d)exposing said sample to an applied magnetic field; and, (e) measuring achange in a nuclear relaxation property of said sample caused by saidinteraction between said FPP and said biochemical molecular species ormolecules, in the applied magnetic field; wherein a change in T.sub.1nuclear relaxation property is correlated to the presence of said targetbiochemical molecular species in said sample, further wherein said FPPcomprises a particle made of a non ferrous oxide paramagnetic core.

It is a further embodiment of the present invention to provide a methodfor characterizing a target biochemical molecular species in a sample,comprising; (a) providing a sample; (b) providing FunctionalizedParamagnetic Particles (FPP) adapted to interact with said targetbiochemical molecular species, each FPP comprising at least oneparamagnetic core and at least one moiety that is adapted to interactwith said target biochemical molecular species; (c) contacting said FPPwith said sample under conditions that allow the interaction betweensaid FPP and said target biochemical molecular species; (d) exposingsaid sample to an applied magnetic field; and, (e) measuring a change ina nuclear relaxation property of said sample caused by said interactionbetween said FPP and said target biochemical molecular species in theapplied magnetic field; wherein a change in T.sub.1 nuclear relaxationproperty is correlated to at least one characteristic of said targetbiochemical molecular species in said sample, further wherein said FPPcomprises a non ferrous oxide paramagnetic core or paramagnetic species.

It is further within the scope of the present invention that theanalyzed samples are either solid, liquid gas or a combination thereof.Especially, the analyzed sample may comprise a biological fluid, abiological tissue, a tissue extract, an industrial fluid, food sample, abeverage, wine, water and any combination thereof.

More specifically, a biological fluid sample may derived, for example,of urine, blood, plasma, lymph, cerebrospinal fluid, saliva, amnioticfluid, bile and tears.

It is also in the scope of the present invention to provide the methodas defined above, further comprising steps of performing two or moremeasurements to determine the relaxation time of the sample, wherein themeasurements are performed before and after at least one addition ofsaid FPP.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of detecting said targetbiochemical molecular species and/or characterizing at least oneproperty correlated with the occurrence of said biochemical molecularspecies in vitro.

It is still in the scope of the present invention to provide the methodas defined above, wherein said FPP are formed as a single molecule, amultimeric system, a micro-sized vesicle or particle, a nano-sizedvesicle or particle, a liposome, a probe or any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting said samplefrom a group consisting of a liquid, a gas, a slurry, a liquidcontaining particulates, a gas containing particulates, a gel, a sol, asuspension, a solution, a dispersion, a colloid, a mixture, an emulsion,an aerosol, a liquid containing solid objects, a gas containing solidobjects, and any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of selecting said sample froma group comprising a biological fluid, a biological tissue, a tissueextract, an industrial fluid, food sample, a beverage, wine, water,potable water, sewage, irrigation water, sea water, river water, lakewater, industrial effluent, farm effluent, effluent from humanhabitation, road runoff, cleaning fluid, a gas sample or any combinationthereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of selecting said biologicalfluid from a group comprising urine, blood, plasma, lymph, cerebrospinalfluid, saliva, amniotic fluid, bile and tears.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of providing said samplewithin a production process.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting saidproduction process in an industrial area, said industrial area is amember of a group consisting of the pharmaceuticals, food production,beverage production, chemical refining, chemical processing, medicalproducts, biological products, metal casting, metal refining,desalination, fluid purification, and sewage processing.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of analyzing at least onecharacteristic or property of said target molecular species selectedfrom a group comprising concentration, permeability, oxidation state,redox characteristic (reduction-oxidation state), activation state andany combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of applying a magnetic field,thereby enhancing a change in a paramagnetic nuclear relaxation propertyof said sample upon comparing relaxation rates at two different magneticfields.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of measuring a change in anuclear relaxation property of said sample using a portable NMR or MRImeasuring means.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of measuring a change in anuclear relaxation property of said sample using a magnetic resonancedevice (MRD) consisting of magnets housed within a cage.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of measuring a change in anuclear relaxation property of said sample using a self-fastening cagetype of a magnetic resonance device (MRD) (300).

According to a further embodiment of the present invention, in aself-fastening cage of a magnetic resonance device (MRD) (300), a methodas defined above further comprises steps of providing a homogeneous,stable and uniform magnetic field therein, further wherein saidself-fastening cage type MRD additionally characterized by an outsideshell comprising at least three flexi-jointed superimposed walls (1).

According to a further embodiment of the present invention, in aself-fastening cage type MRD (300), a method as defined above furthercomprises steps of providing an MRD characterized by an outside shell;said outside shell comprising at least three flexi-jointed superimposedwalls (1) disposed in a predetermined clockwise or counterclockwisearrangement; said MRD comprising: (a) at least six side-magnets (2)arranged in two equal groups being in a face-to-face orientation in amagnetic connection with said outside shell, increasing the overallstrength of the magnetic field provided in said cage; (b) at least twopole-magnet pieces (3), arranged in a face-to-face orientation inbetween said side-magnets (2); (c) at least two main-magnets (4),located on said pole-pieces (3), arranged in a face-to-face orientation,generating the static magnetic field therein said cage; and, (d)shimming mechanism, said mechanism is selected from a group consistingof an array of active shim coils, passive shimming elements or acombination thereof; wherein at least a portion of said side-magnets (2)are superconductors or ferromagnets.

It is further in the scope of the present invention to provide amagnetic resonance device (MRD) comprising: a means of producing alarge, uniform magnetic field around a sample, such as a large permanentmagnet and shimming mechanism selected from active or passive shimmingelements; a means of producing a magnetic field gradient around thesample; and a magnetic resonance sensing probe comprising an inductancecoil and capacitor connected to a radio antenna.

It is still in the scope of the present invention to provide the methodas defined above, wherein said applied magnetic field comprises amagnetic resonance signal level in the range of about 0.1 Tesla andabout 10 Tesla.

It is still in the scope of the present invention to provide the methodas defined above, further comprises steps of applying a magneticresonance frequency in the range of about 5 MHz to about 40 MHz.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of providing a magneticresonance device adapted to producing high contrast high resolutionimages of said sample.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of providing a magneticresonance device comprising: (a) an envelope for least partiallyconfining said sample; (b) a plurality of magnets located at leastpartially around said envelope; and, (c) a CPU to process said imagescomprising a computer readable medium containing instructions forgenerating at least one third image superimposing at least one image ofsaid first images with at least one image of said second images. In aspecific embodiment, the plurality of magnets comprising: (a) a leastone first magnet configured to provide a high magnetic field forgenerating multiple time-resolved one or more first images at highresolution of at least a portion of said sample; and (b) a least onesecond magnet configured to provide a low magnetic field for generatingmultiple time-resolved one or more second images at high contrast of atleast portion of same said sample; wherein at least one image of saidfirst images and at least one image of said second images beinggenerated in a time no greater than approximately the time between twofirst images.

It is still in the scope of the present invention to provide the methodas defined above, comprising additional steps of: (a) generatingmultiple time resolved one or more first images at high resolution of atleast a portion of said sample; (b) generating multiple time resolvedone or more second images at high contrast of at least portion of samesaid sample; and (c) superimposing at least one image of said firstimages with at least one image of said second images; whereby ahigh-contrast, high resolution real-time continuous image of said sampleis obtained.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting said atleast one first magnet to be of 2 Tesla and lower.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting said atleast one first magnet to be of 2 Tesla and higher.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting said atleast one first magnet from a group consisting of permanent magnets,electromagnets, superconducting magnets, and any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting said atleast one second magnet to be of 2 Tesla and lower.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting said atleast one second magnet to be of 2 Tesla and higher.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting said atleast one second magnet from a group consisting of permanent magnets,electromagnets, superconducting magnets, and any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of selecting saidmagnets from a group consisting of permanent magnets, electromagnets,superconducting magnets, and any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of selecting said moiety froma group comprising antibodies, antibody fragments, monoclonal antibody,receptors, ligands, macromolecules, peptides, hormones, fatty acids,lipids, receptor agonists and antagonists, amino acids, sugars, lectins,albumins, polycarbon molecules, glycoproteins, nucleic acids, pegylatedmolecules, liposomes, chelators, cells, viruses, chemotherapeutic agentsand any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of detecting and/or analysinga target molecular species selected from a group comprising a biologicalmolecule, a chemical molecule, an analyte, a contaminant, a particle, apathogen or any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of selecting said targetbiochemical molecular species from a group comprising a protein, apathogen, a prion, a virus, a bacteria, a contaminant, a pathologicalisoform, a biomarker, an allergen, a neurotransmitter, an antigenicdeterminant, an epitope, a cell marker, cell membrane marker or epitope,a membrane marker, an enzyme, a chemical molecule, an analyte, areceptor, a ligand, a macromolecule, a peptide, a hormone, a fatty acid,a lipid, a receptor agonist and antagonist, an amino acid, a sugar, aglycoprotein, a nucleic acid, an antioxidant agent, a chemotherapeuticagent, a biological tissue and any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of selecting said analytefrom a group comprising an organic analyte and an inorganic analyte.

It is still in the scope of the present invention to provide the methodas defined above, wherein said inorganic analyte is molecular oxygen oran oxygen-containing molecule or oxygen containing radicals andcombinations thereof.

It is still in the scope of the present invention to provide the methodas defined above, comprising an additional step of detectingoxygen-containing radicals “ad hoc” generated, for assessing theanti-oxidant properties of the sample.

It is still in the scope of the present invention to provide the methodas defined above, wherein said paramagnetic core is a metal ion, oxidesof a metal ion, oxides of a transition metal, mixed oxides of atransition metal and their mixtures.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of selecting said metal ionfrom a group comprising an ion (except for iron oxide) of nickel,manganese, copper, gadolinium, dysprosium, europium and mixturesthereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of selecting saidparamagnetic core or species loaded in the FPP from a group comprisingmetal complexes, aggregated of metal complexes, polymer-bound metalcomplexes, stable organic radicals and mixtures thereof.

It is still in the scope of the present invention to provide the methodas defined above, based on a competition assay for assessing oxygenconsumption or redox characteristics, comprising steps of detectingdifferences in Paramagnetic Relaxation Enhancement (PRE) propertiesinduced by a change in at least one redox characteristic of said FPP,using an applied magnetic field.

It is still in the scope of the present invention to provide the methodas defined above, further comprises steps of selecting said redoxcharacteristic from a group comprising lipid peroxidation, lipidperoxidation followed by a change in membrane permeability, redoxpotential of metal ions, formation and cleavage of disulfide bonds,oxidation state, antioxidant activity and any combination thereof.

It is still in the scope of the present invention to provide the methodas defined above, further comprises a step of providing said FPP as aliposome loaded with a plurality of paramagnetic cores or payloads.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of applying a magnetic field,thereby enhancing a change in the permeability of said liposome so as toaffect a nuclear relaxation property of said sample.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of applying a magnetic field,thereby enhancing a change in at least one of cleavage or formation ofdisulfide bonds of said moiety so as to affect a nuclear relaxationproperty of said sample.

It is still in the scope of the present invention to provide the methodas defined above, further comprising steps of applying a magnetic field,thereby affecting at least one property of said FPP selected from agroup comprising concentration, lipid peroxidation, membranepermeability, redox potential, formation and cleavage of disulfidebonds, oxidation state, redox potential, activation state, bindingaffinity, and any combination thereof, so as to induce a change in anuclear relaxation property of said sample.

It is still in the scope of the present invention to provide the methodas defined above, further comprises steps of conjugating said liposomewith a site-specific ligand.

It is still in the scope of the present invention to provide the methodas defined above, further comprises steps of conjugating said liposomewith a biotin activated molecule.

It is still in the scope of the present invention to provide the methodas defined above, further comprises steps of providing said FPP as abiotinylated liposome.

According to a further embodiment, the present invention provides amethod for detection of a biomarker in a sample whose main component iswater, comprising steps of: (a) obtaining a sample; (b) providingliposomes loaded with a plurality of paramagnetic agents, said liposomesare conjugated with a site specific moiety configured to interact withsaid biomarker in said sample; (c) contacting said liposomes with saidsample under conditions that allow the interaction between the sitespecific moiety and said biomarker; (d) exposing said sample to anapplied magnetic field; and, (e) measuring a change in a nuclearrelaxation property of said sample caused by said interaction betweenthe liposomes and said biomarker in the applied magnetic field; whereina change in T.sub.1 nuclear relaxation property is correlated to thepresence of said biomarker in said sample.

It is still in the scope of the present invention to provide the methodas defined above, further comprises the steps of: (a) providingbiotinylated liposomes; said liposomes loaded with a plurality ofparamagnetic agents; (b) providing biotinylayed ligands, said ligandsconfigured to interact with said biomarker; (c) providing activatedavidin molecules; (d) contacting said biotinylated liposomes, saidbiotinylayed ligands and said activated avidin molecules with saidsample so as to enable avidin-biotin interaction, thereby formingcomplexes comprising said liposomes, said ligand and said biomarker;such that said complexes are specific to said biomarker; and, (e)measuring a change in a nuclear relaxation property of said samplecaused by said complex formation in the applied magnetic field; whereina change in T.sub.1 nuclear relaxation property is correlated to thepresence of said biomarker in said sample.

In a further embodiment, the present invention provides a system fordetecting a target biochemical molecular species or at least oneproperty correlated with the occurrence of said biochemical molecularspecies in a sample, especially a sample whose main component is water,said system comprising; (a) a magnetic resonance device (MRD) configuredto measure a change in nuclear relaxation property of said sample; and,(b) a plurality of Functionalized Paramagnetic Particles (FPP)configured to interact with said target biochemical molecular species ofsaid sample, each of said FPP comprising a paramagnetic core and amoiety configured to interact with said target biochemical molecularspecies, or with molecules collectively reporting on a property of saidtarget biochemical molecular species; wherein a change in T.sub.1nuclear relaxation property measured by said MRD is correlated to thepresence of said FPP and said biochemical molecular species and/or atleast one property correlated with the occurrence of said biochemicalmolecular species in said sample, thereby detecting the presence of saidtarget biochemical molecular species in said sample, further whereinsaid FPP comprises a non ferrous oxide paramagnetic core.

In a further embodiment the present invention provides a use ofFunctionalized Paramagnetic Particles (FPP) configured to interact witha predetermined target biochemical molecular species or a biomarkerwithin a sample, to detect the presence or at least one othercharacteristic of said target biochemical molecular species orbiomarker, each of said FPP comprising a paramagnetic core and a moietyconfigured to interact with said target biochemical molecular species orwith molecules collectively reporting on a property of said targetbiochemical molecular species; wherein a change in T.sub.1 nuclearrelaxation property measured by a generated applied magnetic field iscorrelated to the presence or at least one other characteristic of saidtarget biochemical molecular species in said sample.

In a further embodiment, the present invention provides a method ofestablishing the redox potential of a production batch or continuousflow of a Foodstuff, Beverage or Wine (FBW), or of a biological fluid,comprising the steps of: (a) obtaining a sample removed from saidproduction batch or continuous flow of said FBW or from a biologicalfluid; (b) providing Functionalized Paramagnetic Particles (FPP)configured to change their redox potential upon interaction withdissolved molecular oxygen or to active radicals “ad hoc” generated insaid removed sample; (c) contacting said FPP with said removed sample;(d) exposing said removed sample to an applied magnetic field; and, (e)measuring a change in a nuclear relaxation property of said removedsample caused by said change in the redox potential or antioxidantproperties of said FPP in the applied magnetic field; wherein a changein T.sub.1 nuclear relaxation property is correlated with theconcentration of said molecular oxygen or of radicals of said removedsample, thereby establishing the redox potential or the anti-oxidantability of said production batch or continuous flow of said FBW or ofsaid biological fluid.

It is also within the scope of the present invention to provide themethod as described above, further comprising the step of providing saidFPP conjugated with at least one moiety configured to interact withdissolved molecular oxygen on the “ad hoc” generated radicals.

It is still within the scope of the present invention to provide themethod as described above, further comprising the step of selecting saidmoiety from a group comprising a lipid, a fatty acid, an amino acid, apeptide, a protein, a molecule containing at least one disulfide bond, aliposome and any combination thereof.

It is still within the scope of the present invention to provide themethod as described above, further comprising the step of measuring achange in a nuclear relaxation property of said sample caused by achange in the antioxidant activity of said removed sample in the appliedmagnetic field.

It is still within the scope of the present invention to provide themethod as described above, further comprising the step of measuring adifference in Paramagnetic Relaxation Enhancement (PRE) property of saidremoved sample caused by said interaction of said FPP with saiddissolved molecular oxygen or said “ad hoc” generated radicals.

It is still within the scope of the present invention to provide themethod as described above, further comprising the step of contactingsaid removed sample with FPP configured to form a liposome structure,said FPP comprising a paramagnetic core and a fatty acid moiety, whereinperoxidation of said fatty acid moiety substantially changes thepermeability of said liposome.

It is still within the scope of the present invention to provide themethod as described above, further comprising the step of measuring achange in a nuclear relaxation property of said removed sample based oncompetition for molecular oxygen consumption.

It is still within the scope of the present invention to provide themethod as described above, further comprising the step of contactingsaid removed sample with FPP comprising a metal ion, oxides of a metalion, oxides of a transition metal, mixed oxides of a transition metaland their mixtures or paramagnetic species.

It is still within the scope of the present invention to provide themethod as described above, further comprising steps of selecting saidmetal ion from a group comprising an ion of nickel, manganese, copper,gadolinium, dysprosium, europium and mixtures thereof.

It is a further embodiment of the present invention to provide a systemfor establishing the redox potential of a production batch or continuousflow of a Foodstuff, Beverage or Wine (FBW), comprising: (a) a magneticresonance device (MRD) configured to measure a change in a nuclearrelaxation property of a sample removed from said production batch orcontinuous flow of said FBW; and, (b) a plurality of FunctionalizedParamagnetic Particles (FPP) configured to be in contact with saidremoved sample, said plurality of FPP are further configured to changetheir redox potential upon interaction with dissolved molecular oxygenof said removed sample; wherein a change in T.sub.1 nuclear relaxationproperty measured by said MRD is correlated to the concentration ofdissolved molecular oxygen of said removed sample of said productionbatch or continuous flow of said FBW, thereby establishing the oxidativestate of said production batch or continuous flow of said FBW.

It is a further embodiment of the present invention to provide a systemfor establishing the potability of a production batch or continuous flowof a flowable Foodstuff, Beverage or Wine (FBW), comprising: (a) amagnetic resonance device (MRD) configured to measure a change innuclear relaxation property of a sample removed from said productionbatch or continuous flow of said FBW; and, (b) a plurality offunctionalized paramagnetic particles (FPP) configured to be in contactwith said sample, said plurality of FPP are further configured to changetheir redox potential upon interaction with dissolved molecular oxygenor the “ad hoc” generated radicals of said removed sample; wherein achange in T.sub.1 nuclear relaxation property measured by said MRDcorrelates with dissolved molecular oxygen or the “ad hoc” generatedradical concentration of said FBW sample, thereby establishing thepotability of said production batch or continuous flow of said FBW.

It is herein acknowledged that the anti-oxidant ability in wine,beverage, foodstuff or in biological fluids changes over time becausethe oxygen and oxygen contained species are used in oxidative reactions.Thus according to specific embodiments of the invention, the system ofthe present invention is further adapted to establish the anti-oxidantproperties of a foodstuff, wine, beverage or biological fluid sample.

It is further within the scope of the present invention that the term‘hedonic scale’ refers to a commonly used and acceptable scale used infood science, marketing research and tasting panels where therespondents indicate the extent to which they either like or dislikefood or beverage. The hedonic scale is often used for assessing thequality of wine. Hedonic scales commonly range from 2 (like, dislike) to7 points. It is reported that commonly, an average person is able toreliably distinguish between no more than 7-9 degrees of perfection ofquality trait. One example of such a scale is the five-point hedonicscale, which include the following degrees: like very much, like, isacceptable, do not like, strongly do not like. The hedonic scale is auniversal scale, which is used in the determination of the degree ofperfection of the assessed elements of quality, as well as clarifyingthe views of consumers about the quality of the product.

It is also within the scope of the present invention to provide thesystem as defined above, wherein a value lower than X ml of Oxygen perliter is correlated to >7 of the 9 point hedonic scale.

It is also within the scope of the present invention to provide thesystem as defined above, wherein a value lower than X ml of Oxygen perliter is correlated to >y of the hybrid scale.

It is also within the scope of the present invention to provide thesystem as defined above, wherein a value lower than X ml of Oxygen perliter is correlated to >y of the self-adjusting scale.

In a further embodiment, the system and method of the present inventionis applicable for assessment of anti-oxidant property of a sample ofinterest. Such a sample may be derived of a biological fluid, abiological tissue, a tissue extract, an industrial fluid, food sample, abeverage, wine, water, a gas sample or any combination thereof.

According to certain aspects, the anti-oxidant property may be assessedby measuring the redox characteristics of a sample i.e. detecting andquantifying ad hoc generated radicals. For this end paramagneticparticles i.e. FPP comprising a paramagnetic agent linked to a molecularprobe may be used.

One optional approach to evaluate the redox characteristics of a sampleusing the method and system of the present invention is by measuring thelipid peroxidation activity or properties of the sample. This can beachieved by using a paramagnetic probe or FPP comprising a paramagneticspecies i.e. Gd which is functionalized with a covalently linked fattyacid moiety i.e. linolenic acid. The transformation of the redoxcharacteristics of the fatty acid moiety may be followed by a T1 change.Such a magnetic resonance effect may reflect the differences inParamagnetic relaxation enhancement (PRE) property caused by theinteraction of the sample with the macromolecular paramagnetic system.

According to an alternative approach, the paramagnetic probe i.e.comprising a Gd entity linked to a fatty acid moiety is a part of aliposome structure. In such a case, the peroxidation of the fatty acidmoiety may change the permeability of the liposome membrane and thusaffect the measured nuclear relaxation property of the sample.

According to yet another embodiment, the assessment of anti-oxidantproperty of a sample of interest may be performed using methods based oncompetition for oxygen consumption or redox characteristics. In such anexample the FPP complex as disclosed herein above may contain a metalion such as Mn(II) as a paramagnetic species, that upon interaction withhyperoxide or superoxide radicals transforms its oxidation state i.e. toMn (III). The change in the oxidation state of the paramagnetic speciesmay generate T1 effect in ¹H-relaxometric assay measured by NMR or MRItechnique. According to yet another embodiment, the anti-oxidantproperty of a sample of interest may be assessed using a paramagnetic(i.e. Gd) complex where the measured T1 is dependent on the formationand cleavage of disulfide (s-s) bonds within the functionalizedmacromolecular probe linked to the paramagnetic moiety.

Reference is now made to FIG. 1 showing a schematic representation of asystem and procedure, for detection of a predetermined epitope orreceptor, on a cell membrane, using the targeted functionalizedparamagnetic particles or probes (FPP) of the present invention. Such asystem and method can be useful, for example, for assessment of folatereceptors within a biological sample. In this figure, the paramagneticprobe is a liposome 100 loaded with a plurality of paramagnetic speciesor cores 30. In this embodiment, the liposome 100 is conjugated with atarget moiety 10 through a spacer 20, which may comprise for example apegylated chain. The target moiety 10 can be a ligand (i.e. folic acidor a folic acid derivative) that is adapted to interact or bind with itscorresponding receptor 50 (i.e. folate receptor) that may be located onthe cellular surface or membrane 70 of a cell 200. The target moiety 10is allowed to bind with the receptor 50 and the non bound liposomes arethen removed. The sample, which includes the bound liposomes loaded withparamagnetic species, is exposed to an applied magnetic field configuredto measure a change in nuclear relaxation property of the sample. Thechange in the measured T.sub.1 nuclear relaxation property in theapplied magnetic field indicates the presence of the specific receptorin the analysed sample. Furthermore, the difference in the measuredParamagnetic Relaxation Enhancement (PRE) properties is correlated withthe concentration of the receptor within the tested sample.

According to a further embodiment, the paramagnetic core 30, embeddedwithin the liposome membrane, comprise Mn(II) ions. In a specificexample, each liposome is loaded with about 4*10⁵ Mn(II) ions. In afurther embodiment, the target moiety 10, which is conjugated to theliposome membrane, is folate. In such an example, about 9*10⁵ folateresidues are exposed per liposome. In a cell binding experiment usingHuman Ovarian Cancer cells (IGROV-1) overexpressing folate receptors 50at the cell membrane 70, about 5000 liposomes were found to be bound toeach cell. In such an embodiment, the total cell surface is covered byliposomes, thus it is difficult to discriminate between cells withdifferent receptor expression level.

Reference is now made to FIG. 2 showing schematic representation of amulti step procedure, using the functionalized paramagnetic particles orprobes of the present invention, for detection of a predeterminedepitope or receptor, on a cell membrane. In such an embodiment,biotinylated liposomes 100 are prepared, containing about 10⁵paramagnetic centers 30 per liposome and biotin residues 60 conjugatedwith the liposome membrane by a spacer 20. The biotinylated liposomesare added to a sample containing cells 200 expressing folate receptors50 at their membrane surface 70, activated streptavidin molecules 80,and folic acid residues 10 linked to biotin residues 60. The sitespecific residues (i.e. biotin-streptavidin and folic acidresidues-folate receptors) are allowed to specifically bind to eachother and a subsequent washing step of unbound residues is followed. Thesample containing the bound paramagnetic liposomes is then exposed to amagnetic field and a change in a nuclear relaxation property (i.e. T1and/or T2) of the sample is measured. The aforementioned change in anuclear relaxation property (i.e. T1 and/or T2) of the sample iscorrelated with the presence and/or concentration of the targetmolecule, for example the expressed folate receptors on a cellularmembranes.

It is thus one embodiment of the present invention to provide anefficient self-fastening cage of a MRD (300) for providing ahomogeneous, stable and uniform magnetic field therein, characterized byan outside shell comprising at least three flexi-jointed superimposedmetal alloy walls (1).

It is also in the scope of the present invention to provide theaforementioned MRD further comprising at least six side-magnets (2)arranged in two equal groups configured in a face-to-face orientation,in a magnetic connection with the cage walls (1), increasing the overallstrength of the magnetic field provided in said cage; at least twopole-pieces (3), arranged in a face-to-face orientation in betweenside-magnets (2); and, at least two main-magnets (4), located on saidpole-pieces (3), arranged in a face-to-face orientation, generating thestatic magnetic field therein said cage.

Reference is made now to FIG. 7, schematically presenting a partialsectional top and out of scale view, with respect to an axial plane ofthe 3D MRD (300) wherein the shape of a square parallelepiped isprovided, having four cage walls (1), four side magnets (2); and apole-piece (3); said cage walls and side-magnets are essentiallyinterconnected in a superimposed manner such that a self-fastening cageis obtained.

Reference is made now to FIG. 8, schematically presenting an entireperspective view of the of the 3D MRD, having two cage walls (1), eightside magnets (2); two pole-pieces (3); two main magnet (4) and eightsquare corner-magnets (5) and four cylinder corner-magnets locatedinside the pole-pieces; all of them are arranged in two equal groupsface-to-face orientation.

In another embodiment, a high contrast, high resolution magneticresonance device i.e. MRI is provided. A non-limiting example of anembodiment of this type is schematically illustrated in FIG. 4. Thedevice (400) comprises two sets of magnets (420, 430). The RF coils (notshown) are part of an envelope (440) which contains the sample to beanalyzed (410). In this embodiment, the high magnetic field magnets(420) are in a horizontal orientation, while the low magnetic fieldmagnets (430) are in a vertical orientation. In other embodiments, thelow field magnets can be inside the high magnetic field magnets. In yetother embodiments, the low magnetic field magnets can be outside thehigh magnetic field magnets. Such embodiments can be used in the methodsand systems as disclosed herein.

EXAMPLES

Various examples were carried out to prove the embodiments claimed inthe present invention. Some of these experiments are referredhereinafter. The examples describe the manner and process of the presentinvention and set forth the best mode contemplated by the inventors forcarrying out the invention, but are not to be construed as limiting theinvention.

Example 1 Assessment of Anti-Oxidant Activity (AOA) in Liquid orBeverage Samples, Such as Wine or Spirits or Liquors

It is herein acknowledged that AOA prevents lipid peroxidation. In thisembodiment, the paramagnetic-probe complex that is used, contains a Gdparamagnetic core that is functionalized with a linoleinic acid moiety(L). Upon interaction of the GD complex (GD-L), with oxygen-basedradicals, lipid peroxide products are produced, as schematically shownin the following reaction:

Gd-L→Gd-LO2.→products

The aforementioned lipid transformation process can be followed byT1-change, which may exploit and reflect differences in ParamagneticRelaxation Enhancement (PRE) upon interaction with the macromolecularparamagnetic complex system.

In an alternative embodiment, Gd-L is part of a liposome structure; theperoxidation of L changes the permeability of the liposome membrane andthus affects the measured T.sub.1 nuclear relaxation property of thesample.

In an alternative embodiment, competition assays for oxygen consumptionand/or redox characteristics are used, based on the system and method asherein described. Such systems may comprise a Mn(II)-containingparamagnetic probe that transforms into a Mn(III) complex. Thistransformation may result a T1 nuclear relaxation property effect. In afurther example, such a system may comprise a Gd macromolecular complexor probe, where T1 is dependent on the formation and/or cleavage ofdisulfide (S—S) bonds within the macromolecular probe.

Example 2 Assessment of Epitopes on Cell Membranes

Reference is now made to FIG. 3 schematically describing a furtherembodiment of the method for assessment of cell receptors using thefunctionalized paramagnetic particles (FPP) of the present invention. Inthis embodiment, paramagnetic functionalized liposomes, for exampleparamagnetic particles as described in FIG. 1 or FIG. 2, are incubatedwith a sample containing cells suspected to express a receptor ofinterest. Following a washing step of unbound liposomes, disruption ofthe bound liposome sample, for example by a sonication procedure, isperformed. In a further specific embodiment, Human Serum Albumin (HSA)(about 40 mg/ml) is added to the disrupted cell sample containing thesuspended paramagnetic cores. A relaxometric measurement is thenperformed for determining PRE properties of the sample. The change inPRE as compared with a control sample indicates the presence and/orconcentration of the tested target epitope, for example a cell receptor.

Reference is now made to FIG. 4 showing a graphic representation of therelaxometric measurement results over extended range of frequencies(MHz). As can be seen, after sonication and addition of HSA (40 mg/ml)to the sample containing cells expressing a specific epitope andfunctionalized paramagnetic liposomes adapted to interact with theepitope, as described above, a specific peak in the relaxativity valuewas shown in the rage of frequencies of about 20-40 MHz.

In order to evaluate the affect of the concentration of the paramagneticagent used in the FPP, samples containing different Mn(II) ionconcentration, undergone liposome sonication and HSA (40 mg/ml)addition, were exposed to electromagnetic frequencies of 20 MHz and weresubjected to a relaxometric measurement. Reference is now made to FIG.5, showing a graphic representation of relaxation rate measurementresults at different Mn(II) ion concentration. As can be seen in thisfigure, a direct correlation was observed between concentrations of theparamagnetic core (i.e. Mn(II) ions) used within the FPP, and themeasured relation rate. It can be further concluded that a value ofabout 5 μM Mn concentration was the lowest detectable Mn(II) ionconcentration.

The above described experiment shows that Mn(II) ion concentration of[Mn]=5 mM corresponds to 1.5×10⁹ liposome particles in 200 μl. In oneembodiment, the number of liposome particles (FPP) is calculatedaccording to the following equation:

No. of receptors per cell×No of cells≧1.5×10⁹

Thus, in the case of 1×10⁶ receptors per cell, 1500 cells are necessaryto enable detection of a desirable expressed receptor using the minimalrequired concentration of Mn(II) ions containing paramagnetic liposomes.

Example 3 Paramagnetic Liposome Preparation

According to certain embodiments of the present invention,functionalized paramagnetic liposome particles are prepared. The 1^(st)step of the process may include the preparation of thin lipidic film. Inone embodiment, the film comprises the following ingredients (20 mg/ml):

DPPC 77% Cholesterol 20% DSPE-methoxy-PEG2000  2% DSPE-target moiety(i.e. folate)-PEG2000  1%

Reference is now made to FIG. 6 schematically describing optional stepsin the functionalized paramagnetic liposome (FPP) preparation process.In one embodiment, the 2^(nd) step of the process includes the mixing ofthe lipidic film with an isotonic solution containing the Mn(II) ionsand the hydration of the mixture. In the 3^(rd) step, multilamellarvesicles (MLV) are prepared by vortexing the hydrated mixture at 55° C.This step is followed by a 4^(th) step of extrusion at 55° C. to obtainlarge unilamellar vesicles (LUV) with a mean diameter of above 50 nm,preferably between about 120 nm and 140 nm. In the 5^(th) step the LUVpreparation is then subjected to a TET A treatment and dialysis toobtain the functionalized paramagnetic liposomes.

FIGS. 1 to 9 and examples thus establish the applicability and enable,inter alia, each and all which follows:

A novel method for detecting a target biochemical molecular species orat least one property correlated with the occurrence of said biochemicalmolecular species in a sample whose main component is water, comprisingsteps of (a) obtaining a sample whose main component is water; (b)providing Functionalized Paramagnetic Particles (FPP) comprising aparamagnetic core and a moiety configured to interact with said targetbiochemical molecular species or with molecules collectively reportingon a property of said target biochemical molecular species; (c)contacting said FPP with said sample; (d) exposing said sample to anapplied magnetic field; (e) measuring a change in a nuclear relaxationproperty of said sample, caused by said interaction between said FPP andsaid biochemical molecular species or said molecules collectivelyreporting on a property of said target biochemical molecular species; inthe applied magnetic field; and, correlating said change to the presenceof said biochemical molecular species in said sample or to at least oneproperty correlated with the occurrence of said biochemical molecularspecies in said sample; wherein a change in T.sub.1 nuclear relaxationproperty of the water protons in said sample is correlated to thepresence of said target biochemical molecular species or to at least oneproperty correlated with the occurrence of said biochemical molecularspecies in said sample, further wherein said FPP comprises a non ferrousoxide paramagnetic core.

A method as defined in any of the above, comprising at least oneadditional step; said step is selected from a group consisting of one ormore of the following:

-   a. performing two or more measurements to determine the relaxation    time of the sample, wherein the measurements are performed before    and after at least one addition of said FPP;-   b. detecting said target biochemical molecular species and/or    characterizing at least one property correlated with the occurrence    of said biochemical molecular species in vitro;-   c. forming said FPP as a single molecule, a multimeric system, a    micro-sized vesicle or particle, a nano-sized vesicle or particle, a    liposome, a probe or any combination thereof;-   d. selecting said sample from a group consisting of a liquid, a gas,    a slurry, a liquid containing particulates, a gas containing    particulates, a gel, a sol, a suspension, a solution, a dispersion,    a colloid, a mixture, an emulsion, an aerosol, a liquid containing    solid objects, a gas containing solid objects, and any combination    thereof;-   e. selecting said sample from a group comprising a biological fluid,    a biological tissue, a tissue extract, an industrial fluid, food    sample, a beverage, wine, water, potable water, sewage, irrigation    water, sea water, river water, lake water, industrial effluent, farm    effluent, effluent from human habitation, road runoff, cleaning    fluid, a gas sample or any combination thereof;-   f. selecting said biological fluid from a group comprising urine,    blood, lymph, plasma, cerebrospinal fluid, saliva, amniotic fluid,    bile and tears;-   g. providing said sample within a production process;-   h. selecting said production process in an industrial area, said    industrial area is a member of a group consisting of the    pharmaceuticals, food production, beverage production, chemical    refining, chemical processing, medical products, biological    products, metal casting, metal refining, desalination, fluid    purification, and sewage processing;-   i. analyzing at least one characteristic or property of said target    molecular species, said characteristic or property is selected from    a group comprising concentration, permeability, oxidation state,    redox characteristic (reduction-oxidation state), activation state    and any combination thereof;-   j. applying a magnetic field, thereby enhancing the change in a    paramagnetic nuclear relaxation property of said sample upon    comparing relaxation rates at two different magnetic fields;-   k. measuring a change in a nuclear relaxation property of said    sample using a portable NMR or MRI measuring means;-   l. measuring a change in a nuclear relaxation property of said    sample using a magnetic resonance device (MRD) consisting of magnets    housed within a cage; and-   m. measuring a change in a nuclear relaxation property of said    sample using a self-fastening cage type of a magnetic resonance    device (MRD).

In a self-fastening cage of a magnetic resonance device (MRD) (300), amethod according to claim 1 comprising at least one additional step;said step is selected from a group consisting of one or more of thefollowing:

-   a. providing a homogeneous, stable and uniform magnetic field    therein, further wherein said self-fastening cage type MRD    additionally characterized by an outside shell comprising at least    three flexi-jointed superimposed walls (1);-   b. providing an MRD characterized by an outside shell; said outside    shell comprising at least three flexi-jointed superimposed walls (1)    disposed in a predetermined clockwise or counterclockwise    arrangement; said MRD comprising: at least six side-magnets (2)    arranged in two equal groups being in a face-to-face orientation in    a magnetic connection with said outside shell, increasing the    overall strength of the magnetic field provided in said cage; at    least two pole-magnet pieces (3), arranged in a face-to-face    orientation in between said side-magnets (2); at least two    main-magnets (4), located on said pole-pieces (3), arranged in a    face-to-face orientation, generating the static magnetic field    therein said cage; and, shimming mechanism, said mechanism is    selected from a group consisting of an array of active shim coils,    passive shimming elements or a combination thereof; wherein at least    a portion of said side-magnets (2) are superconductors or    ferromagnets;-   c. providing a magnetic resonance device adapted to producing high    contrast high resolution images of said sample;-   d. providing a magnetic resonance device comprising: an envelope for    least partially confining said sample; a plurality of magnets    located at least partially around said envelope, said plurality of    magnets comprising: a least one first magnet configured to provide a    high magnetic field for generating multiple time-resolved one or    more first images at high resolution of at least a portion of said    sample; and a least one second magnet configured to provide a low    magnetic field for generating multiple time-resolved one or more    second images at high contrast of at least portion of same said    sample; wherein at least one image of said first images and at least    one image of said second images being generated in a time no greater    than approximately the time between two first images; and, a CPU to    process said images comprising a computer readable medium containing    instructions for generating at least one third image superimposing    at least one image of said first images with at least one image of    said second images;-   e. generating multiple time resolved one or more first images at    high resolution of at least a portion of said sample; generating    multiple time resolved one or more second images at high contrast of    at least portion of same said sample; and then superimposing at    least one image of said first images with at least one image of said    second images; whereby a high-contrast, high resolution real-time    continuous image of said sample is obtained;-   f. selecting said at least one first magnet to be of 2 Tesla and    lower;-   a. selecting said at least one first magnet to be of 2 Tesla and    higher;-   b. said at least one first magnet from a group consisting of    permanent magnets, electromagnets, superconducting magnets, and any    combination thereof;-   c. selecting said at least one second magnet to be of 2 Tesla and    lower;-   d. selecting said at least one second magnet to be of 2 Tesla and    higher;-   e. selecting said at least one second magnet from a group consisting    of permanent magnets, electromagnets, superconducting magnets, and    any combination thereof;-   f. generating a magnetic resonance signal in the range of about 0.1    Tesla and about 10 Tesla;-   g. generating a magnetic resonance signal in the range of 2 Tesla    and lower;-   h. generating a magnetic resonance signal in the range of 2 Tesla    and higher;-   i. applying a magnetic resonance frequency in the range of about 5    MHz to about 40 MHz;-   j. selecting said magnets from a group consisting of permanent    magnets, electromagnets, superconducting magnets, and any    combination thereof;-   k. selecting said moiety from a group comprising antibodies,    antibody fragments, monoclonal antibody, receptors, ligands,    macromolecules, peptides, hormones, fatty acids, lipids, receptor    agonists and antagonists, amino acids, sugars, lectins, albumins,    polycarbon molecules, glycoproteins, nucleic acids, pegylated    molecules, liposomes, chelators, cells, viruses, chemotherapeutic    agents and any combination thereof;-   l. selecting said target biochemical molecular species from a group    comprising a biological molecule, a chemical molecule, an analyte, a    contaminant, a particle, a pathogen or any combination thereof;-   m. selecting said target biochemical molecular species from a group    comprising a protein, a pathogen, a prion, a virus, a bacteria, a    contaminant, a pathological isoform, a biomarker, an allergen, a    neurotransmitter, an antigenic determinant, an epitope, a cell    marker, cell membrane marker or epitope, a membrane marker, an    enzyme, a chemical molecule, an analyte, a receptor, a ligand, a    macromolecule, a peptide, a hormone, a fatty acid, a lipid, a    receptor agonist and antagonist, an amino acid, a sugar, a    glycoprotein, a nucleic acid, an antioxidant agent, a    chemotherapeutic agent, a biological tissue and any combination    thereof;-   n. selecting said analyte from a group comprising an organic analyte    and an inorganic analyte;-   o. selecting said inorganic analyte from a group comprising    molecular oxygen, oxygen-containing radicals and combinations    thereof; detecting oxygen-containing radicals “ad hoc” generated,    for assessing the anti-oxidant properties of the sample;-   p. selecting said paramagnetic core as a metal ion, a metal complex,    oxides of a metal ion, oxides of a transition metal, mixed oxides of    a transition metal and their mixtures;-   q. selecting said paramagnetic core from a group comprising metal    complexes, aggregates of metal complexes, polymer-bound metal    complexes, stable organic radicals and any combination thereof;-   r. selecting said metal ion from a group comprising an ion of    nickel, iron, manganese, copper, gadolinium, europium and mixtures    thereof;-   s. assessing redox characteristics, comprising steps of detecting    differences in Paramagnetic Relaxation Enhancement (PRE) properties    induced by a change in at least one redox characteristic of said    FPP, using an applied magnetic field;-   t. selecting said redox characteristic from a group comprising lipid    peroxidation, lipid peroxidation followed by a change in membrane    permeability, redox potential of metal ions, formation and cleavage    of disulfide bonds, oxidation state, antioxidant activity and any    combination thereof;-   u. providing said FPP as a liposome loaded with a plurality of    paramagnetic payloads;-   v. applying a magnetic field, thereby enhancing a change in the    permeability of said liposome so as to affect a nuclear relaxation    property of said sample;-   w. applying a magnetic field, thereby enhancing a change in at least    one of cleavage or formation of disulfide bonds of said moiety so as    to affect a nuclear relaxation property of said sample;-   x. applying a magnetic field, thereby affecting at least one    property of said FPP selected from a group comprising concentration,    lipid peroxidation, membrane permeability, redox potential,    formation and cleavage of disulfide bonds, oxidation state, redox    potential, activation state, binding affinity, and any combination    thereof, so as to induce a change in a nuclear relaxation property    of said sample;-   y. conjugating said liposome with a site-specific ligand;-   z. conjugating said liposome with a biotin activated molecule; and-   aa. providing said FPP as a biotinylated liposome.

A method for detection of a biomarker in a sample whose main componentis water, comprising steps as follows:

-   a. obtaining a sample whose main component is water;-   b. providing liposomes loaded with a plurality of paramagnetic    agents, said liposomes are conjugated with a site specific moiety    configured to interact with said biomarker in said sample;-   c. contacting said liposomes with said sample under conditions that    allow the interaction between the site specific moiety and said    biomarker;-   d. exposing said sample to an applied magnetic field; and,-   e. measuring a change in a nuclear relaxation property of said    sample caused by said interaction between the liposomes and said    biomarker in the applied magnetic field;    wherein a change in T.sub.1 nuclear relaxation property is    correlated to the presence of said biomarker in said sample.

A method as defined above, wherein the method further comprising one ormore steps as follows:

-   a. providing biotinylated liposomes; said liposomes loaded with a    plurality of paramagnetic agents;-   b. providing biotinylayed ligands, said ligands configured to    interact with said biomarker;-   c. providing activated avidin molecules;-   d. contacting said biotinylated liposomes, said biotinylayed ligands    and said activated avidin molecules with said sample so as to enable    avidin-biotin interaction, thereby forming complexes comprising said    liposomes, said ligand and said biomarker; such that said complexes    are specific to said biomarker; and,-   e. measuring a change in a nuclear relaxation property of said    sample caused by said complex formation in the applied magnetic    field;    wherein a change in T.sub.1 nuclear relaxation property is    correlated to the presence of said biomarker in said sample.

A system for detecting a target biochemical molecular species or atleast one property correlated with the occurrence of said biochemicalmolecular species in a sample whose main component is water, comprisinga magnetic resonance device (MRD) configured to measure a change innuclear relaxation property of said sample; and, a plurality ofFunctionalized Paramagnetic Particles (FPP) said FPP comprising aparamagnetic core and a moiety configured to interact with said targetbiochemical molecular species or with molecules collectively reportingon a property of said target biochemical molecular species; wherein achange in T.sub.1 nuclear relaxation property of water protons in saidsample measured by said MRD is correlated to the presence of said targetbiochemical molecular species and/or to the at least one propertycorrelated with the occurrence of said biochemical molecular species insaid sample, further wherein said FPP comprises a non-ferrous oxideparamagnetic core.

The system as defined above wherein the system further comprising meansfor detecting said target biochemical molecular species and/orcharacterizing at least one property correlated with the occurrence ofsaid biochemical molecular species in vitro.

The system as defined in any of the above, wherein the FPP is formed asa single molecule, a multimeric system, a micro-sized vesicle orparticle, a nano-sized vesicle or particle, a liposome, a probe and anycombination thereof.

The system as defined in any of the above, wherein the sample isselected from a group consisting of a liquid, a gas, a slurry, a liquidcontaining particulates, a gas containing particulates, a gel, a sol, asuspension, a solution, a dispersion, a colloid, a mixture, an emulsion,an aerosol, a liquid containing solid objects, a gas containing solidobjects, and any combination thereof.

The system as defined in any of the above, wherein the sample is furtherselected from a group comprising a biological fluid, a biologicaltissue, a tissue extract, an industrial fluid, food sample, a beverage,wine, water, potable water, sewage, irrigation water, sea water, riverwater, lake water, industrial effluent, farm effluent, effluent fromhuman habitation, road runoff, cleaning fluid, a gas sample or anycombination thereof.

The system as defined in any of the above, wherein the biological fluidis selected from a group comprising urine, blood, lymph, plasma,cerebrospinal fluid, saliva, amniotic fluid, bile and tears.

The system as defined in any of the above, wherein the sample isprovided within a production process.

The system as defined in any of the above, wherein the productionprocess is in an industrial area, said industrial area is a member of agroup consisting of the pharmaceuticals, food production, beverageproduction, chemical refining, chemical processing, medical products,biological products, metal casting, metal refining, desalination, fluidpurification, and sewage processing.

The system as defined in any of the above, wherein the property isselected from a group comprising concentration, permeability, oxidationstate, redox characteristic (reduction-oxidation state), activationstate and any combination thereof.

The system as defined in any of the above, wherein the magneticresonance device (MRD) is configured to enhance the change in aparamagnetic nuclear relaxation property of said sample upon comparingrelaxation rates at two different magnetic fields.

The system as defined in any of the above, wherein the magneticresonance device (MRD) is a portable NMR or MRI measuring means.

The magnetic resonance device (MRD) consists of magnets housed within acage.

The system as defined in any of the above, wherein the magneticresonance device (MRD) is a self-fastening cage type of a magneticresonance device (300).

In a self-fastening cage of a magnetic resonance device (MRD) (300), asystem as defined above, wherein said self-fastening cage type MRDadditionally characterized by an outside shell comprising at least threeflexi-jointed superimposed walls (1).

In a self-fastening cage type MRD (300), a system as defined above, saidsystem further comprises an MRD characterized by an outside shell; saidoutside shell comprising at least three flexi-jointed superimposed walls(1) disposed in a predetermined clockwise or counterclockwisearrangement; said MRD comprising: at least six side-magnets (2) arrangedin two equal groups being in a face-to-face orientation in a magneticconnection with said outside shell, increasing the overall strength ofthe magnetic field provided in said cage; at least two pole-magnetpieces (3), arranged in a face-to-face orientation in between saidside-magnets (2); at least two main-magnets (4), located on saidpole-pieces (3), arranged in a face-to-face orientation, generating thestatic magnetic field therein said cage; and, a shimming mechanism, saidmechanism is selected from a group consisting of an array of active shimcoils, passive shimming elements or a combination thereof; wherein atleast a portion of said side-magnets (2) are superconductors orferromagnets.

The system as defined in any of the above, wherein the MRD is configuredto produce high contrast high resolution images of said sample.

The system as defined in any of the above, wherein the magneticresonance device comprising an envelope for least partially confiningsaid sample; a plurality of magnets located at least partially aroundsaid envelope, said plurality of magnets comprising: a least one firstmagnet configured to provide a high magnetic field for generatingmultiple time-resolved one or more first images at high resolution of atleast a portion of said sample; and a least one second magnet configuredto provide a low magnetic field for generating multiple time-resolvedone or more second images at high contrast of at least portion of samesaid sample; wherein at least one image of said first images and atleast one image of said second images being generated in a time nogreater than approximately the time between two first images; and, a CPUto process said images comprising a computer readable medium containinginstructions for generating at least one third image superimposing atleast one image of said first images with at least one image of saidsecond images, whereby a high contrast, high resolution real timecontinues image of said sample is obtained.

The system as defined in any of the above wherein at least one of thefollowing is held true: said at least one first magnet is of 2 Tesla andlower; said at least one first magnet is of 2 Tesla and higher; said atleast one first magnet is selected from a group consisting of permanentmagnets, electromagnets, superconducting magnets, and any combinationthereof; said at least one second magnet is of 2 Tesla and lower; saidat least one second magnet is of 2 Tesla and higher; at least one secondmagnet is selected from a group consisting of permanent magnets,electromagnets, superconducting magnets, and any combination thereof;said magnetic resonance device (MRD) is configured to generate amagnetic resonance signal in the range of about 0.1 Tesla and about 10Tesla; said magnetic resonance device (MRD) is configured to generate amagnetic resonance signal in the range of 2 Tesla and lower; saidmagnetic resonance device (MRD) is configured to generate a magneticresonance signal in the range of 2 Tesla and higher; said magneticresonance device (MRD) is configured to generate a magnetic resonancefrequency in the range of about 5 MHz to about 40 MHz; said magnets areselected from a group consisting of permanent magnets, electromagnets,superconducting magnets, and any combination thereof; said moiety isselected from a group comprising antibodies, antibody fragments,monoclonal antibody, receptors, ligands, macromolecules, peptides,hormones, fatty acids, lipids, receptor agonists and antagonists, aminoacids, sugars, lectins, albumins, polycarbon molecules, glycoproteins,nucleic acids, pegylated molecules, liposomes, chelators, cells,viruses, chemotherapeutic agents and any combination thereof; saidtarget biochemical molecular species is selected from a group comprisinga biological molecule, a chemical molecule, an analyte, a contaminant, aparticle, a pathogen or any combination thereof; said target biochemicalmolecular species is selected from a group comprising a protein, apathogen, a prion, a virus, a bacteria, a contaminant, a pathologicalisoform, a biomarker, an allergen, a neurotransmitter, an antigenicdeterminant, an epitope, a cell marker, cell membrane marker or epitope,a membrane marker, an enzyme, a chemical molecule, an analyte, areceptor, a ligand, a macromolecule, a peptide, a hormone, a fatty acid,a lipid, a receptor agonist and antagonist, an amino acid, a sugar, aglycoprotein, a nucleic acid, an antioxidant agent, a chemotherapeuticagent, a biological tissue and any combination thereof. said analyte isselected from a group comprising an organic analyte and an inorganicanalyte; said inorganic analyte is selected from a group comprisingmolecular oxygen, oxygen-containing radicals and combinations thereof;said oxygen-containing radicals are “ad hoc” generated radicals, forassessing the anti-oxidant properties of the sample; said paramagneticcore is selected from a group comprising a metal ion, a metal complex,oxides of a metal ion, oxides of a transition metal, mixed oxides of atransition metal and their mixtures; said metal ion is selected from agroup comprising an ion of nickel, iron, manganese, copper, gadolinium,europium and mixtures thereof; said redox characteristic is selectedfrom a group comprising lipid peroxidation, lipid peroxidation followedby a change in membrane permeability, redox potential of metal ions,formation and cleavage of disulfide bonds, oxidation state, antioxidantactivity and any combination thereof; said FPP is a liposome loaded witha plurality of paramagnetic payloads; said system further comprisingmeans for enhancing a change in the permeability of said liposome so asto affect a nuclear relaxation property of said sample; said system isadapted to detect a change in at least one of cleavage or formation ofdisulfide bonds of said moiety so as to affect a nuclear relaxationproperty of said sample; said property correlated with the occurrence ofsaid biochemical molecular species is selected from a group comprisingconcentration, lipid peroxidation, membrane permeability, redoxpotential, formation and cleavage of disulfide bonds, oxidation state,redox potential, activation state, binding affinity, and any combinationthereof; said liposome is conjugated with a site-specific ligand; saidliposome is conjugated with a biotin activated molecule; and said FPP isa biotinylated liposome.

A system for detection of a biomarker in a sample whose main componentis water, comprising: a sample whose main component is water; liposomesloaded with a plurality of paramagnetic agents, said liposomes areconjugated with a site specific moiety configured to interact with saidbiomarker in said sample; a magnetic resonance device (MRD) configuredto measure a change in a nuclear relaxation property of a sample whosemain component is water removed from said production batch or continuousflow of said FBW or biological fluid; wherein a change in T.sub.1nuclear relaxation property of the water protons in said sample iscorrelated to the presence of said biomarker in said sample.

Use of Functionalized Paramagnetic Particles (FPP) to detect thepresence or at least one other characteristic of a target biochemicalmolecular species within a sample whose main component is water, saidFPP comprising a paramagnetic core and a moiety configured to interactwith said target biochemical molecular species or with moleculescollectively reporting on a property of said target biochemicalmolecular species; wherein a change in T.sub.1 nuclear relaxationproperty of water protons within said sample measured by a generatedapplied magnetic field is correlated to the presence or at least oneother characteristic of said target biochemical molecular species insaid sample.

The use as defined above further adapted to detect at least one propertycorrelated with the occurrence of said biochemical molecular species insaid sample.

A method of establishing the redox properties of a production batch orcontinuous flow of a Foodstuff, Beverage or Wine (FBW) or of abiological fluid, comprising the steps of obtaining a sample removedfrom said production batch or continuous flow of said FBW or from saidbiological fluid; providing Functionalized Paramagnetic Particles (FPP)configured to change their redox property upon interaction withdissolved molecular oxygen or “ad hoc” generated radicals of saidremoved sample; contacting said FPP with said removed sample; exposingsaid removed sample to an applied magnetic field; and, measuring achange in a nuclear relaxation property of said removed sample caused bysaid change in the redox properties of said FPP in the applied magneticfield; wherein a change in T.sub.1 nuclear relaxation property iscorrelated with the presence and/or concentration of said molecularoxygen or of the “ad hoc” generated radicals of said removed sample,thereby establishing the redox properties of said production batch orcontinuous flow of said FBW or of said biological fluid.

The method as defined above, wherein the method further comprising atleast one step, said step or steps is/are selected from a groupconsisting of the following: providing said FPP conjugated with at leastone moiety configured to interact with dissolved molecular oxygen orwith “ad hoc” generated radicals; selecting said moiety from a groupcomprising a lipid, a fatty acid, an amino acid, a peptide, a protein, amolecule containing at least one disulfide bond, a liposome and anycombination thereof; measuring a change in a nuclear relaxation propertyof said sample caused by a change in the antioxidant activity of saidremoved sample in the applied magnetic field; measuring a difference inParamagnetic Relaxation Enhancement (PRE) property of said removedsample caused by said interaction of said FPP with said dissolvedmolecular oxygen or with said “ad hoc” generated radicals; contactingsaid removed sample with FPP configured to form a liposome structure,said FPP comprising a paramagnetic core and a fatty acid moiety, whereinperoxidation of said fatty acid moiety substantially changes thepermeability of said liposome; measuring a change in a nuclearrelaxation property of said removed sample based on competition formolecular oxygen consumption; providing said FPP comprising aparamagnetic core selected from a group comprising a metal ion, a metalcomplex, oxides of a metal ion, oxides of a transition metal, mixedoxides of a transition metal and their mixtures; selecting said metalion from a group comprising an ion of nickel, iron, manganese, copper,gadolinium, dysprosium, europium and mixtures thereof; and selectingsaid biological fluid from a group comprising urine, blood, lymph,plasma, cerebrospinal fluid, saliva, amniotic fluid, bile and tears.

A system for establishing the redox properties of a production batch orcontinuous flow of a Foodstuff, Beverage, Wine (FBW) or of a biologicalfluid, comprising: a magnetic resonance device (MRD) configured tomeasure a change in a nuclear relaxation property of a sample removedfrom said production batch or continuous flow of said FBW or of saidbiological fluid; and, a plurality of Functionalized ParamagneticParticles (FPP) configured to be in contact with said removed sample,said plurality of FPP are further configured to change at least one oftheir redox properties upon interaction with dissolved molecular oxygenor with “ad hoc” generated radicals of said removed sample; wherein achange in T.sub.1 nuclear relaxation property measured by said MRD iscorrelated to the presence or concentration of dissolved molecularoxygen or “ad hoc” generated radicals of said removed sample, therebythe redox properties of said production batch or continuous flow of saidFBW or of said biological fluid are established.

The system according as defined above, wherein said biological fluid isselected from a group comprising urine, blood, lymph, plasma,cerebrospinal fluid, saliva, amniotic fluid, bile and tears.

A system for establishing the potability of a production batch orcontinuous flow of a flowable Foodstuff, Beverage or Wine (FBW),comprising: a magnetic resonance device (MRD) configured to measure achange in nuclear relaxation property of a sample removed from saidproduction batch or continuous flow of said flowable FBW; and, aplurality of functionalized paramagnetic particles (FPP) configured tobe in contact with said sample, said plurality of FPP are furtherconfigured to change their redox/oxidative properties upon interactionwith dissolved molecular oxygen or “ad hoc” generated radicals of saidremoved sample; wherein a change in T.sub.1 nuclear relaxation propertymeasured by said MRD correlates with dissolved molecular oxygen or “adhoc” generated radicals concentration of said FBW sample, therebyestablishing the potability of said production batch or continuous flowof said flowable FBW.

The system according as defined above, wherein at least one of thefollowing is held true: a concentration value lower than about 6 ml ofdissolved oxygen per liter of said removed sample is indicative of thepotability of said production batch or continuous flow of said FBW; avalue lower than X ml of oxygen per liter is correlated to >7 of the 9point hedonic scale; a value lower than X ml of oxygen per liter iscorrelated to >y of the hybrid scale; and a value lower than X ml ofoxygen per liter is correlated to >y of the self-adjusting scale.

What is claimed is:
 1. A method for detecting a target biochemicalmolecular species in a sample whose main component is water, comprisingthe steps of: a. obtaining a sample whose main component is water; b.providing Functionalized Paramagnetic Particles (FPP) comprising aparamagnetic core and a moiety configured to interact with said targetbiochemical molecular species; c. contacting said FPP with said sample;d. exposing said sample to an applied magnetic field; e. measuring achange in a nuclear relaxation property of said sample, caused by saidinteraction between said FPP and said biochemical molecular species inthe applied magnetic field with a magnetic resonance device (MRD); andf. correlating said change to the presence of said biochemical molecularspecies in said sample; wherein a change in T.sub.1 nuclear relaxationproperty of the water protons in said sample is correlated to thepresence of said target biochemical molecular species; and wherein saidFPP comprises a non ferrous oxide paramagnetic core.
 2. The methodaccording to claim 1, comprising at least one additional step selectedfrom the group consisting of: performing two or more measurements todetermine the relaxation time of the sample, wherein the measurementsare performed before and after at least one addition of said FPP;detecting said target biochemical molecular species in vitro; formingsaid FPP as a single molecule, a multimeric system, a micro-sizedvesicle or particle, a nano-sized vesicle or particle, a liposome, aprobe or any combination thereof; selecting said sample from a groupconsisting of a liquid, a gas, a slurry, a liquid containingparticulates, a gas containing particulates, a gel, a sol, a suspension,a solution, a dispersion, a colloid, a mixture, an emulsion, an aerosol,a liquid containing solid objects, a gas containing solid objects, andany combination thereof; selecting said sample from a group comprising abiological fluid, a biological tissue, a tissue extract, an industrialfluid, food sample, a beverage, wine, water, potable water, sewage,irrigation water, sea water, river water, lake water, industrialeffluent, farm effluent, effluent from human habitation, road runoff,cleaning fluid, a gas sample or any combination thereof; selecting saidbiological fluid from a group comprising urine, blood, lymph, plasma,cerebrospinal fluid, saliva, amniotic fluid, bile and tears; providingsaid sample within a production process in an industry selected frompharmaceuticals production, food production, beverage production,chemical refining, chemical processing, medical products, biologicalproducts, metal casting, metal refining, desalination, fluidpurification, and sewage processing; applying a magnetic field, therebyenhancing the change in a paramagnetic nuclear relaxation property ofsaid sample upon comparing relaxation rates at two different magneticfields; measuring a change in a nuclear relaxation property of saidsample using a portable NMR or MRI measuring means; measuring a changein a nuclear relaxation property of said sample using a magneticresonance device (MRD) consisting of magnets housed within a cage; andmeasuring a change in a nuclear relaxation property of said sample usinga self-fastening cage type of a magnetic resonance device (MRD).
 3. Amethod according to claim 1, wherein said change in nuclear relaxationproperty is measured using a self-fastening cage magnetic resonancedevice (MRD), and comprising at least one additional step selected fromthe group consisting of: providing a homogeneous, stable and uniformmagnetic field therein, further wherein said self-fastening cage typeMRD is additionally characterized by an outside shell comprising atleast three flexi-jointed superimposed walls; providing an MRDcharacterized by an outside shell, said outside shell comprising atleast three flexi-jointed superimposed walls disposed in a predeterminedclockwise or counterclockwise arrangement, said MRD comprising at leastsix side-magnets arranged in two equal groups being in a face-to-faceorientation in a magnetic connection with said outside shell, increasingthe overall strength of the magnetic field provided in said cage; atleast two pole-magnet pieces, arranged in a face-to-face orientation inbetween said side-magnets; at least two main-magnets, located on saidpole-pieces, arranged in a face-to-face orientation, generating thestatic magnetic field in said cage; and shimming mechanism, saidmechanism selected from the group consisting of an array of active shimcoils, passive shimming elements or a combination thereof; wherein atleast a portion of said side-magnets (2) are superconductors orferromagnets; providing a magnetic resonance device adapted to producinghigh contrast high resolution images of said sample; providing amagnetic resonance device comprising: an envelope for least partiallyconfining said sample; a plurality of magnets located at least partiallyaround said envelope, said plurality of magnets comprising: a least onefirst magnet configured to provide a high magnetic field for generatingmultiple time-resolved one or more first images at high resolution of atleast a portion of said sample; and a least one second magnet configuredto provide a low magnetic field for generating multiple time-resolvedone or more second images at high contrast of at least portion of samesaid sample; wherein at least one image of said first images and atleast one image of said second images being generated in a time nogreater than approximately the time between two first images; and, a CPUto process said images comprising a computer readable medium containinginstructions for generating at least one third image superimposing atleast one image of said first images with at least one image of saidsecond images; generating multiple time resolved one or more firstimages at high resolution of at least a portion of said sample;generating multiple time resolved one or more second images at highcontrast of at least portion of same said sample; and then superimposingat least one image of said first images with at least one image of saidsecond images; whereby a high-contrast, high resolution real-timecontinuous image of said sample is obtained; selecting said at least onefirst magnet to be of 2 Tesla and lower; selecting said at least onefirst magnet to be of 2 Tesla and higher; said at least one first magnetfrom a group consisting of permanent magnets, electromagnets,superconducting magnets, and any combination thereof; selecting said atleast one second magnet to be of 2 Tesla and lower; selecting said atleast one second magnet to be of 2 Tesla and higher; selecting said atleast one second magnet from a group consisting of permanent magnets,electromagnets, superconducting magnets, and any combination thereof;generating a magnetic resonance signal in the range of about 0.1 Teslaand about 10 Tesla; generating a magnetic resonance signal in the rangeof 2 Tesla and lower; generating a magnetic resonance signal in therange of 2 Tesla and higher; applying a magnetic resonance frequency inthe range of about 5 MHz to about 40 MHz; selecting said magnets from agroup consisting of permanent magnets, electromagnets, superconductingmagnets, and any combination thereof; selecting said moiety from a groupcomprising antibodies, antibody fragments, monoclonal antibody,receptors, ligands, macromolecules, peptides, hormones, fatty acids,lipids, receptor agonists and antagonists, amino acids, sugars, lectins,albumins, polycarbon molecules, glycoproteins, nucleic acids, pegylatedmolecules, liposomes, chelators, cells, viruses, chemotherapeutic agentsand any combination thereof; selecting said target biochemical molecularspecies from a group comprising a biological molecule, a chemicalmolecule, an analyte, a contaminant, a particle, a pathogen or anycombination thereof; selecting said target biochemical molecular speciesfrom a group comprising a protein, a pathogen, a prion, a virus, abacteria, a contaminant, a pathological isoform, a biomarker, anallergen, a neurotransmitter, an antigenic determinant, an epitope, acell marker, cell membrane marker or epitope, a membrane marker, anenzyme, a chemical molecule, an analyte, a receptor, a ligand, amacromolecule, a peptide, a hormone, a fatty acid, a lipid, a receptoragonist and antagonist, an amino acid, a sugar, a glycoprotein, anucleic acid, an antioxidant agent, a chemotherapeutic agent, abiological tissue and any combination thereof; selecting said analytefrom a group comprising an organic analyte and an inorganic analyte;selecting said inorganic analyte from a group comprising molecularoxygen, oxygen-containing radicals and combinations thereof; detectingoxygen-containing radicals “ad hoc” generated, for assessing theanti-oxidant properties of the sample; selecting said paramagnetic coreas a metal ion, a metal complex, oxides of a metal ion, oxides of atransition metal, mixed oxides of a transition metal and their mixtures;selecting said paramagnetic core from a group comprising metalcomplexes, aggregates of metal complexes, polymer-bound metal complexes,stable organic radicals and any combination thereof; selecting saidmetal ion from a group comprising an ion of nickel, iron, manganese,copper, gadolinium, europium and mixtures thereof; assessing redoxcharacteristics, comprising steps of detecting differences inParamagnetic Relaxation Enhancement (PRE) properties induced by a changein at least one redox characteristic of said FPP, using an appliedmagnetic field; selecting said redox characteristic from a groupcomprising lipid peroxidation, lipid peroxidation followed by a changein membrane permeability, redox potential of metal ions, formation andcleavage of disulfide bonds, oxidation state, antioxidant activity andany combination thereof; providing said FPP as a liposome loaded with aplurality of paramagnetic payloads; applying a magnetic field, therebyenhancing a change in the permeability of said liposome so as to affecta nuclear relaxation property of said sample; applying a magnetic field,thereby enhancing a change in at least one of cleavage or formation ofdisulfide bonds of said moiety so as to affect a nuclear relaxationproperty of said sample; applying a magnetic field, thereby affecting atleast one property of said FPP selected from a group comprisingconcentration, lipid peroxidation, membrane permeability, redoxpotential, formation and cleavage of disulfide bonds, oxidation state,redox potential, activation state, binding affinity, and any combinationthereof, so as to induce a change in a nuclear relaxation property ofsaid sample; conjugating said liposome with a site-specific ligand;conjugating said liposome with a biotin activated molecule; andproviding said FPP as a biotinylated liposome.
 4. A method for detectionof a biomarker in a sample whose main component is water, comprising thesteps of: obtaining a sample whose main component is water; providingliposomes loaded with a plurality of paramagnetic agents, said liposomesconjugated with a site specific moiety configured to interact with saidbiomarker in said sample; contacting said liposomes with said sampleunder conditions that allow the interaction between the site specificmoiety and said biomarker; exposing said sample to an applied magneticfield; and measuring a change in a nuclear relaxation property of saidsample caused by said interaction between the liposomes and saidbiomarker in the applied magnetic field; wherein a change in T.sub.1nuclear relaxation property is correlated to the presence of saidbiomarker in said sample.
 5. The method according to claim 4, comprisingadditional steps of: providing biotinylated liposomes; said liposomesloaded with a plurality of paramagnetic agents; providing biotinylatedligands, said ligands configured to interact with said biomarker;providing activated avidin molecules; contacting said biotinylatedliposomes, said biotinylated ligands and said activated avidin moleculeswith said sample so as to enable avidin-biotin interaction, therebyforming complexes comprising said liposomes, said ligand and saidbiomarker; such that said complexes are specific to said biomarker; and,measuring a change in a nuclear relaxation property of said samplecaused by said complex formation in the applied magnetic field; whereina change in T.sub.1 nuclear relaxation property is correlated to thepresence of said biomarker in said sample.
 6. The method according toclaim 4, wherein said sample is selected from a group consisting of aliquid, a gas, a slurry, a liquid containing particulates, a gascontaining particulates, a gel, a sol, a suspension, a solution, adispersion, a colloid, a mixture, an emulsion, an aerosol, a liquidcontaining solid objects, a gas containing solid objects, and anycombination thereof.
 7. A system for detection of a biomarker in asample whose main component is water, comprising: a. a sample whose maincomponent is water; b. liposomes loaded with a plurality of paramagneticagents, said liposomes conjugated with a site specific moiety configuredto interact with said biomarker in said sample; c. a magnetic resonancedevice (MRD) configured to measure a change in a nuclear relaxationproperty of the sample whose main component is water removed from aproduction batch or continuous flow of said FBW or biological fluid;wherein a change in T.sub.1 nuclear relaxation property of the waterprotons in said sample is correlated to the presence of said biomarkerin said sample.
 8. A method of establishing the redox properties of aproduction batch or continuous flow of a Foodstuff, Beverage or Wine(FBW) or of a biological fluid, comprising the steps of: a. obtaining asample removed from said production batch or continuous flow of said FBWor from said biological fluid; b. providing Functionalized ParamagneticParticles (FPP) configured to change their redox property uponinteraction with dissolved molecular oxygen or ad hoc generated radicalsof said removed sample; c. contacting said FPP with said removed sample;d. exposing said removed sample to an applied magnetic field; and, e.measuring a change in a nuclear relaxation property of said removedsample caused by said change in the redox properties of said FPP in theapplied magnetic field; wherein a change in T.sub.1 nuclear relaxationproperty is correlated with the presence and/or concentration of saidmolecular oxygen or of the ad hoc generated radicals of said removedsample, thereby establishing the redox properties of said productionbatch or continuous flow of said FBW or of said biological fluid.
 9. Themethod according to claim 8, wherein said method further comprises atleast one step selected from the group consisting of the following: d.providing said FPP conjugated with at least one moiety configured tointeract with dissolved molecular oxygen or with ad hoc generatedradicals; e. selecting said moiety selected from the group consisting ofa lipid, a fatty acid, an amino acid, a peptide, a protein, a moleculecontaining at least one disulfide bond, a liposome, and any combinationthereof; f. measuring a change in a nuclear relaxation property of saidsample caused by a change in the antioxidant activity of said removedsample in the applied magnetic field; g. measuring a difference inParamagnetic Relaxation Enhancement (PRE) property of said removedsample caused by said interaction of said FPP with said dissolvedmolecular oxygen or with said “ad hoc” generated radicals; h. contactingsaid removed sample with FPP configured to form a liposome structure,said FPP comprising a paramagnetic core and a fatty acid moiety, whereinperoxidation of said fatty acid moiety substantially changes thepermeability of said liposome; i. measuring a change in a nuclearrelaxation property of said removed sample based on competition formolecular oxygen consumption; providing said FPP comprising aparamagnetic core selected from a group comprising a metal ion, a metalcomplex, oxides of a metal ion, oxides of a transition metal, mixedoxides of a transition metal and their mixtures; j. selecting said metalion from a group comprising an ion of nickel, iron, manganese, copper,gadolinium, dysprosium, europium and mixtures thereof; and k. selectingsaid biological fluid from a group comprising urine, blood, lymph,plasma, cerebrospinal fluid, saliva, amniotic fluid, bile and tears. 10.A system for establishing the redox properties of a production batch orcontinuous flow of a Foodstuff, Beverage, Wine (FBW) or of a biologicalfluid, comprising: l. a magnetic resonance device (MRD) configured tomeasure a change in a nuclear relaxation property of a sample removedfrom said production batch or continuous flow of said FBW or of saidbiological fluid; and m. a plurality of Functionalized ParamagneticParticles (FPP) configured to be in contact with said removed sample,said plurality of FPP are further configured to change at least one oftheir redox properties upon interaction with dissolved molecular oxygenor with “ad hoc” generated radicals of said removed sample; wherein achange in T.sub.1 nuclear relaxation property measured by said MRD iscorrelated to the presence or concentration of dissolved molecularoxygen or “ad hoc” generated radicals of said removed sample, therebythe redox properties of said production batch or continuous flow of saidFBW or of said biological fluid are established.
 11. The systemaccording to claim 10, wherein said biological fluid is selected fromthe group consisting of urine, blood, lymph, plasma, cerebrospinalfluid, saliva, amniotic fluid, bile and tears.
 12. A system forestablishing the potability of a production batch or continuous flow ofa flowable Foodstuff, Beverage or Wine (FBW), comprising: a. a magneticresonance device (MRD) configured to measure a change in nuclearrelaxation property of a sample removed from said production batch orcontinuous flow of said flowable FBW; and, b. a plurality offunctionalized paramagnetic particles (FPP) configured to be in contactwith said sample, said plurality of FPP are further configured to changetheir redox/oxidative properties upon interaction with dissolvedmolecular oxygen or ad hoc generated radicals of said removed sample;wherein a change in T.sub.1 nuclear relaxation property measured by saidMRD correlates with dissolved molecular oxygen or ad hoc generatedradicals concentration of said FBW sample, thereby establishing thepotability of said production batch or continuous flow of said flowableFBW.
 13. The system according to claim 12, wherein at least one of thefollowing is held true: a. a concentration value lower than about 6 mlof dissolved oxygen per liter of said removed sample is indicative ofthe potability of said production batch or continuous flow of said FBW;b. a value lower than X ml of oxygen per liter is correlated to >7 ofthe 9 point hedonic scale; c. a value lower than X ml of oxygen perliter is correlated to >y of the hybrid scale; and d. a value lower thanX ml of oxygen per liter is correlated to >y of the self-adjustingscale.